@ARTICLE{Renouf2009-dk, title = "Activation of p53 by {MDM2} antagonists has differential apoptotic effects on {Epstein-Barr} virus ({EBV)-positive} and {EBV-negative} Burkitt's lymphoma cells", author = "Renouf, B and Hollville, E and Pujals, A and T{\'e}taud, C and Garibal, J and Wiels, J", affiliation = "UMR 8126 CNRS, Univ Paris-Sud, Institut Gustave Roussy, Villejuif, France.", abstract = "p53 inactivation is often observed in Burkitt's lymphoma (BL) cells, because of either mutations in p53 gene or an overexpression of the p53-negative regulator MDM2. Epstein-Barr virus (EBV) is present in virtually 100\% of BL cases occurring in endemic areas, but in only 10-20\% of sporadic cases. In EBV(-) BL cells, reactivation of p53, induced by reducing MDM2 protein level, led to apoptosis. We show here that nutlin-3, a potent antagonist of MDM2, activates the p53 pathway in all BL cell lines harboring wild-type p53, regardless of EBV status. However, nutlin-3 strongly induced apoptosis in EBV(-) or latency I EBV(+) cells, whereas latency III EBV(+) cells were much more resistant. Prior treatment with sublethal doses of nutlin-3 sensitizes EBV(-) or latency I EBV(+) cells to apoptosis induced by etoposide or melphalan, but protects latency III EBV(+) cells. p21(WAF1) which is overexpressed in the latter, is involved in this protective effect, as siRNA-mediated inhibition of p21(WAF1) restores sensitivity to etoposide. Nutlin-3 protects latency III BL cells by inducing a p21(WAF1)-mediated G1 arrest. Most BL patients with wild-type p53 tumors could therefore benefit from treatment with nutlin-3, after a careful determination of the latency pattern of EBV in infected patients.", journal = "Leukemia", volume = 23, number = 9, pages = "1557--1563", month = sep, year = 2009, language = "en" } @ARTICLE{Holowaty2004-us, title = "{HAUSP/USP7} as an {Epstein-Barr} virus target", author = "Holowaty, M N and Frappier, L", affiliation = "Department of Medical Genetics and Microbiology, University of Toronto, Toronto, Canada.", abstract = "USP7 (also called HAUSP) is a de-ubiquitinating enzyme recently identified as a key regulator of the p53-mdm2 pathway, which stabilizes both p53 and mdm2. We have discovered that the Epstein-Barr nuclear antigen 1 protein of Epstein-Barr virus binds with high affinity to USP7 and disrupts the USP7-p53 interaction. The results have important implications for the role of Epstein-Barr nuclear antigen 1 in the cellular immortalization that is typical of an Epstein-Barr virus latent infection.", journal = "Biochem. Soc. Trans.", volume = 32, number = "Pt 5", pages = "731--732", month = nov, year = 2004, language = "en" } @ARTICLE{Miller1982-jx, title = "Immortalization of human lymphocytes by {Epstein-Barr} virus", author = "Miller, G", abstract = "Epstein-Barr virus (EBV) confers upon normal lymphocytes derived from bone marrow the ability to proliferate indefinitely in a test tube. This process, called immortalization, is crucial to the pathogenesis of EBV infections. Inside the immortalized lymphocyte the EBV genome exists as a complete multicopy circular plasmid which is probably not integrated into the cell chromosome. Most of the viral genetic information is not expressed. However, at least six to eight separate regions of the EBV genome encode viral products which are made in the immortalized cell. The identification of the function of these few genes holds some interesting answers to questions concerning the biochemical mechanisms of control of lymphocyte growth and differentiation.", journal = "Yale J. Biol. Med.", volume = 55, number = "3-4", pages = "305--310", month = may, year = 1982, language = "en" } @ARTICLE{Cohen2000-kc, title = "{Epstein-Barr} virus infection", author = "Cohen, J I", affiliation = "Medical Virology Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1888, USA. jcohen@niaid.nih.gov", journal = "N. Engl. J. Med.", volume = 343, number = 7, pages = "481--492", month = aug, year = 2000, language = "en" } @ARTICLE{Barsotti2012-nl, title = "p53-Dependent induction of {PVT1} and miR-1204", author = "Barsotti, Anthony M and Beckerman, Rachel and Laptenko, Oleg and Huppi, Konrad and Caplen, Natasha J and Prives, Carol", affiliation = "Department of Biological Sciences, Columbia University, New York, New York 10027, USA.", abstract = "p53 is a tumor suppressor protein that acts as a transcription factor to regulate (either positively or negatively) a plethora of downstream target genes. Although its ability to induce protein coding genes is well documented, recent studies have implicated p53 in the regulation of non-coding RNAs, including both microRNAs (e.g. miR-34a) and long non-coding RNAs (e.g. lincRNA-p21). We have identified the non-protein coding locus PVT1 as a p53-inducible target gene. PVT1, a very large (>300 kb) locus located downstream of c-myc on chromosome 8q24, produces a wide variety of spliced non-coding RNAs as well as a cluster of six annotated microRNAs: miR-1204, miR-1205, miR-1206, miR-1207-5p, miR-1207-3p, and miR-1208. Chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA), and luciferase assays reveal that p53 binds and activates a canonical response element within the vicinity of miR-1204. Consistently, we demonstrate the p53-dependent induction of endogenous PVT1 transcripts and consequent up-regulation of mature miR-1204. Finally, we have shown that ectopic expression of miR-1204 leads to increased p53 levels and causes cell death in a partially p53-dependent manner.", journal = "J. Biol. Chem.", volume = 287, number = 4, pages = "2509--2519", month = jan, year = 2012, language = "en" } @ARTICLE{Raffeld1995-ra, title = "Clustered mutations in the transcriptional activation domain of Myc in 8q24 translocated lymphomas and their functional consequences", author = "Raffeld, M and Yano, T and Hoang, A T and Lewis, B and Clark, H M and Otsuki, T and Dang, C V", affiliation = "Hematopathology Section, National Institutes of Health, Bethesda, MD.", journal = "Curr. Top. Microbiol. Immunol.", volume = 194, pages = "265--272", year = 1995, language = "en" } @ARTICLE{Rabbitts1983-qg, title = "Altered nucleotide sequences of a translocated c-myc gene in Burkitt lymphoma", author = "Rabbitts, T H and Hamlyn, P H and Baer, R", abstract = "The nucleotide sequence of a translocated c-myc gene in a Burkitt lymphoma reveals multiple base changes in the coding region. Twenty-five base changes, generating 16 codon alterations, were found in the first coding exon; no changes occur in the second coding exon. These changes are probably the result of somatic mutations that occurred during and after translocation, and may contribute to oncogenesis by allowing synthesis of an altered c-myc gene product.", journal = "Nature", volume = 306, number = 5945, pages = "760--765", year = 1983, language = "en" } @ARTICLE{Pasqualucci2001-ap, title = "Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphomas", author = "Pasqualucci, L and Neumeister, P and Goossens, T and Nanjangud, G and Chaganti, R S and K{\"u}ppers, R and Dalla-Favera, R", affiliation = "Institute for Cancer Genetics and the Department of Pathology, Columbia University, New York, New York 10032, USA.", abstract = "Genomic instability promotes tumorigenesis and can occur through various mechanisms, including defective segregation of chromosomes or inactivation of DNA mismatch repair. Although B-cell lymphomas are associated with chromosomal translocations that deregulate oncogene expression, a mechanism for genome-wide instability during lymphomagenesis has not been described. During B-cell development, the immunoglobulin variable (V) region genes are subject to somatic hypermutation in germinal-centre B cells. Here we report that an aberrant hypermutation activity targets multiple loci, including the proto-oncogenes PIM1, MYC, RhoH/TTF (ARHH) and PAX5, in more than 50\% of diffuse large-cell lymphomas (DLCLs), which are tumours derived from germinal centres. Mutations are distributed in the 5' untranslated or coding sequences, are independent of chromosomal translocations, and share features typical of V-region-associated somatic hypermutation. In contrast to mutations in V regions, however, these mutations are not detectable in normal germinal-centre B cells or in other germinal-centre-derived lymphomas, suggesting a DLCL-associated malfunction of somatic hypermutation. Intriguingly, the four hypermutable genes are susceptible to chromosomal translocations in the same region, consistent with a role for hypermutation in generating translocations by DNA double-strand breaks. By mutating multiple genes, and possibly by favouring chromosomal translocations, aberrant hypermutation may represent the major contributor to lymphomagenesis.", journal = "Nature", volume = 412, number = 6844, pages = "341--346", month = jul, year = 2001, language = "en" } @ARTICLE{Jiang2012-ah, title = "Genome-wide detection of genes targeted by non-Ig somatic hypermutation in lymphoma", author = "Jiang, Yanwen and Soong, T David and Wang, Ling and Melnick, Ari M and Elemento, Olivier", affiliation = "HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine and Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York, United States of America.", abstract = "The processes of somatic hypermutation (SHM) and class switch recombination introduced by activation-induced cytosine deaminase (AICDA) at the Immunoglobulin (Ig) loci are key steps for creating a pool of diversified antibodies in germinal center B cells (GCBs). Unfortunately, AICDA can also accidentally introduce mutations at bystander loci, particularly within the 5' regulatory regions of proto-oncogenes relevant to diffuse large B cell lymphomas (DLBCL). Since current methods for genomewide sequencing such as Exon Capture and RNAseq only target mutations in coding regions, to date non-Ig promoter SHMs have been studied only in a handful genes. We designed a novel approach integrating bioinformatics tools with next generation sequencing technology to identify regulatory loci targeted by SHM genome-wide. We observed increased numbers of SHM associated sequence variant hotspots in lymphoma cells as compared to primary normal germinal center B cells. Many of these SHM hotspots map to genes that have not been reported before as mutated, including BACH2, BTG2, CXCR4, CIITA, EBF1, PIM2, and TCL1A, etc., all of which have potential roles in B cell survival, differentiation, and malignant transformation. In addition, using BCL6 and BACH2 as examples, we demonstrated that SHM sites identified in these 5' regulatory regions greatly altered their transcription activities in a reporter assay. Our approach provides a first cost-efficient, genome-wide method to identify regulatory mutations and non-Ig SHM hotspots.", journal = "PLoS One", volume = 7, number = 7, pages = "e40332", month = jul, year = 2012, language = "en" } @ARTICLE{Burkitt1962-ts, title = "A ``tumour safari'' in East and Central Africa", author = "Burkitt, D", journal = "Br. J. Cancer", volume = 16, pages = "379--386", month = sep, year = 1962, keywords = "LYMPHOMA", language = "en" } @ARTICLE{Gonzalez-Perez2012-jj, title = "Functional impact bias reveals cancer drivers", author = "Gonzalez-Perez, Abel and Lopez-Bigas, Nuria", affiliation = "Research Programme on Biomedical Informatics - GRIB, Universitat Pompeu Fabra - UPF, Parc de Recerca Biom{\`e}dica de Barcelona. Dr. Aiguader, 88, E-08003 Barcelona, Spain. abel.gonzalez@upf.edu", abstract = "Identifying cancer driver genes and pathways among all somatic mutations detected in a cohort of tumors is a key challenge in cancer genomics. Traditionally, this is done by prioritizing genes according to the recurrence of alterations that they bear. However, this approach has some known limitations, such as the difficulty to correctly estimate the background mutation rate, and the fact that it cannot identify lowly recurrently mutated driver genes. Here we present a novel approach, Oncodrive-fm, to detect candidate cancer drivers which does not rely on recurrence. First, we hypothesized that any bias toward the accumulation of variants with high functional impact observed in a gene or group of genes may be an indication of positive selection and can thus be used to detect candidate driver genes or gene modules. Next, we developed a method to measure this bias (FM bias) and applied it to three datasets of tumor somatic variants. As a proof of concept of our hypothesis we show that most of the highly recurrent and well-known cancer genes exhibit a clear FM bias. Moreover, this novel approach avoids some known limitations of recurrence-based approaches, and can successfully identify lowly recurrent candidate cancer drivers.", journal = "Nucleic Acids Res.", volume = 40, number = 21, pages = "e169", month = nov, year = 2012, language = "en" } @ARTICLE{Puga_L2015-zi, title = "[Intensive chemotherapy for Burkitt lymphoma in {HIV} positive patients]", author = "Puga L, B{\'a}rbara and Bustamante K, Katherinne and Molina E, Javiera and Andrade M, Alejandro", abstract = "BACKGROUND: Burkitt lymphoma has a low incidence, is highly aggressive, may be endemic, sporadic or associated with immunodeficiency and it has a high frequency of extranodal involvement. Overall and relapse free survival in HIV patients is 72 and 71\% respectively. However, the current protocol in Chile considers a positive HIV serology as an exclusion criterion for intensive chemotherapy. AIM: To analyze the response to Burkitt lymphoma treatment among HIV positive patients. MATERIAL AND METHODS: All HIV positive patients with a Burkitt lymphoma treated using PANDA protocol in a public hospital were analyzed. RESULTS: Eight male patients aged between 25 and 43 years, 63\% in stage IV, were analyzed. All patients received an intensified chemotherapy regime, three of them without Rituximab. Complete remission was achieved in 87\%. One patient was refractory to treatment and one patient relapsed at 5 months and died. Overall and relapse free survival were 58 and 60\% respectively. All patients had episodes of high risk febrile neutropenia, but it did not cause deaths. CONCLUSIONS: In this group of HIV patients, intensive chemotherapy for Burkitt lymphoma had a high degree of effectiveness with a low relapse rate and high cure rate.", journal = "Rev. Med. Chil.", volume = 143, number = 12, pages = "1505--1511", month = dec, year = 2015, language = "es" } @ARTICLE{Kojima2014-sg, title = "Clinical outcomes of {AIDS-related} Burkitt lymphoma: a multi-institution retrospective survey in Japan", author = "Kojima, Yuki and Hagiwara, Shotaro and Uehira, Tomoko and Ajisawa, Atsushi and Kitanaka, Akira and Tanuma, Junko and Okada, Seiji and Nagai, Hirokazu", affiliation = "*Department of Hematology, National Hospital Organization Nagoya Medical Center, 4-1-1 Sannomaru, Naka-ku, Nagoya 460-0001, Japan. nagaih@nnh.hosp.go.jp.", abstract = "OBJECTIVE: Acquired immunodeficiency syndrome-related non-Hodgkin lymphoma is treated similarly to non-acquired immunodeficiency syndrome lymphoma, but it is not clear whether highly intensive regimens are beneficial for acquired immunodeficiency syndrome-related Burkitt lymphoma. We conducted a multicenter retrospective survey to clarify the clinical outcomes of acquired immunodeficiency syndrome-related Burkitt lymphoma in the combined antiretroviral therapy era in Japan. METHODS: We retrospectively analyzed the outcome of 33 patients with acquired immunodeficiency syndrome-related Burkitt lymphoma, who were diagnosed at five regional hospitals for human immunodeficiency virus/acquired immunodeficiency syndrome in Japan between January 2002 and December 2010. RESULTS: The median follow-up period was 20.0 months (range 0.5-92.7 months). Six (18.2\%) patients were treated with cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate, ifosphamide, etoposide and high-dose cytarabine, and 23 (69.7\%) patients were treated with hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, high-dose methotrexate and high-dose cytarabine. The overall response rate for all patients was 78.8\%, with a complete response rate of 72.7\%. The two-year overall survival rate was 68.1\%. There was no significant difference in overall survival between chemotherapeutic regimens with rituximab (n = 20) and without rituximab (n = 13) (P = 0.49). The two-year overall survival rate was 66.7\% for patients receiving cyclophosphamide, vincristine, doxorubicin, dexamethasone, etoposide, ifosfamide and cytarabine, and was 72.6\% for patients receiving cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate and cytarabine (P = 0.72). There was one treatment-related death. CONCLUSIONS: Highly intensive chemotherapy would bring a high remission rate and prolonged overall survival for patients with acquired immunodeficiency syndrome-related Burkitt lymphoma.", journal = "Jpn. J. Clin. Oncol.", volume = 44, number = 4, pages = "318--323", month = apr, year = 2014, keywords = "AIDS-related; Burkitt lymphoma; chemotherapy; rituximab; survival", language = "en" } @ARTICLE{Orem2009-dx, title = "Clinical characteristics and outcome of children with Burkitt lymphoma in Uganda according to {HIV} infection", author = "Orem, Jackson and Maganda, Albert and Mbidde, Edward Katongole and Weiderpass, Elisabete", affiliation = "Uganda Cancer Institute, Mulago Hospital and Makerere University School of Medicine, Kampala, Uganda.", abstract = "BACKGROUND: Characteristics of children with Burkitt lymphoma (BL) and HIV infection have not been described in Uganda before. PROCEDURE: We reviewed records at Uganda Cancer Institute (UCI) for years 1994-2004, to compare clinical features and outcome of BL in children who are HIV positive and negative (HIV+, HIV-). As statistical methods we used Student's t-test, Chi-square and Kaplan-Meier's to compare both groups. RESULTS: Of 1,462 records of children retrieved, 228 met the eligibility criteria and were reviewed (158 HIV-, 70 HIV+). There were 139 (61\%) males and 89 (39\%) females. The mean age was 6.9 years (HIV+ 6.7, HIV- 7.1). One hundred seventy-one cases (75\%) had facial tumor (HIV+ 71.4\%, HIV- 76.6\%). HIV positive children presented significantly with extrafacial disease (lymphadenopathy 67\%, hepatic masses 51\%, and thoracic masses 10\%). Presentation with advanced stage disease occurred more frequently in HIV positive patients compared to HIV negative patients. Treatment response rates to chemotherapy were similar irrespective of HIV status. However, overall survival was poorer in HIV positive patients with a median survival of 11.79 months (P-value < 0.000, 95\% CI 8.65-14.92). CONCLUSIONS: BL in Uganda presents frequently with facial disease irrespective of HIV status. However HIV+ BL also presents commonly with extra facial sites, mainly lymphadenopathy. There is no difference in response to treatment with chemotherapy, but HIV+ BL patients have poorer survival. There is need for further characterization of BL in Uganda to understand the role of HIV in disease process and outcome.", journal = "Pediatr. Blood Cancer", volume = 52, number = 4, pages = "455--458", month = apr, year = 2009, language = "en" } @ARTICLE{Buckle2016-hd, title = "Factors influencing survival among Kenyan children diagnosed with endemic Burkitt lymphoma between 2003 and 2011: A historical cohort study", author = "Buckle, Geoffrey and Maranda, Louise and Skiles, Jodi and Ong'echa, John Michael and Foley, Joslyn and Epstein, Mara and Vik, Terry A and Schroeder, Andrew and Lemberger, Jennifer and Rosmarin, Alan and Remick, Scot C and Bailey, Jeffrey A and Vulule, John and Otieno, Juliana A and Moormann, Ann M", affiliation = "Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA. Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, MA. Department of Pediatrics, Hemotology/Oncology, Indiana University School of Medicine, Indianapolis, IN. Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya. Department of Hemotology/Oncology, Indiana University School of Medicine, Indianapolis, IN. Research and Analysis Department, Direct Relief, Goleta, CA. Department of Hematology/Oncology, University of Massachusetts Medical School, Worcester, MA. Department of Oncology and Senior Scientist, Maine Medical Center and Maine Medical Center Research Institute, Portland, ME. Jaramogi Oginga Odinga Teaching and Referral Hospital, Kenya Ministry of Health, Kisumu, Kenya.", abstract = "Discovering how to improve survival and establishing clinical reference points for children diagnosed with endemic Burkitt lymphoma (eBL) in resource-constrained settings has recaptured international attention. Using multivariate analyses, we evaluated 428 children with eBL in Kenya for age, gender, tumor stage, nutritional status, hemoglobin, lactate dehydrogenase (LDH), Epstein-Barr virus (EBV) and Plasmodium falciparum prior to induction of chemotherapy (cyclophosphamide, vincristine, methotrexate and doxorubicin) to identify predictive and prognostic biomarkers of survival. During this 10 year prospective study period, 22\% died in-hospital and 78\% completed six-courses of chemotherapy. Of those, 16\% relapsed or died later; 31\% achieved event-free-survival; and 31\% were lost to follow-up; the overall one-year survival was 45\%. After adjusting for covariates, low hemoglobin (400 mU/ml) were associated with increased risk of death (adjusted Hazard Ratio (aHR) = 1.57 [0.97-2.41]) and aHR = 1.84, [0.91-3.69], respectively). Anemic children with malaria were 3.55 times more likely to die [1.10-11.44] compared to patients without anemia or malarial infection. EBV load did not differ by tumor stage nor was it associated with survival. System-level factors can also contribute to poor outcomes. Children were more likely to die when inadvertently overdosed by more than 115\% of the correct dose of cyclophosphamide (a HR = 1.43 [0.84-2.43]) or doxorubicin (a HR = 1.25, [0.66-2.35]), compared with those receiving accurate doses of the respective agent in this setting. This study codifies risk factors associated with poor outcomes for eBL patients in Africa and provides a benchmark by which to assess improvements in survival for new chemotherapeutic approaches.", journal = "Int. J. Cancer", volume = 139, number = 6, pages = "1231--1240", month = sep, year = 2016, keywords = "Africa; EBV; biomarkers; malaria; pediatric cancer", language = "en" } @ARTICLE{Costa2013-mv, title = "Trends in survival of patients with Burkitt lymphoma/leukemia in the {USA}: an analysis of 3691 cases", author = "Costa, Luciano J and Xavier, Ana C and Wahlquist, Amy E and Hill, Elizabeth G", affiliation = "Division of Hematology and Oncology, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425-6350, USA. costalj@musc.edu", abstract = "It is unknown whether the high rates of cure reported for Burkitt lymphoma/leukemia (BL) patients treated with chemoimmunotherapy can be verified outside published series and clinical trials. We used the Surveillance Epidemiology and End Results (SEER) database to describe time trends in outcomes of BL in the United States. Cases were divided into 2 eras based on year of diagnosis, reflecting improvements in HIV management, BL treatment, and supportive care. There was a marked improvement in survival among BL cases diagnosed in the 2002-2008 era (n = 1922) relative to 1973-2001 (n = 1769) with 5-year relative survival estimates of 56\% and 43\%, respectively (P < .001). Five-year relative survival improved from 71\% to 87\% for ages 0 to 19 (n = 970), 35\% to 60\% for ages 20 to 39 (n = 897), 28\% to 48\% for ages 40 to 59 (n = 1047), and from 25\% to 33\% for ages $\geq$60 (n = 777). In multivariable analysis, the 2002-2008 era (HR = 0.76, P < .001) was associated with lower mortality. Conversely, older age, black race, and advanced stage were associated with higher mortality. More effective therapies are needed for older patients with BL, along with improved access to modern therapy for younger patients.", journal = "Blood", volume = 121, number = 24, pages = "4861--4866", month = jun, year = 2013, language = "en" } @ARTICLE{Sant2010-mu, title = "Incidence of hematologic malignancies in Europe by morphologic subtype: results of the {HAEMACARE} project", author = "Sant, Milena and Allemani, Claudia and Tereanu, Carmen and De Angelis, Roberta and Capocaccia, Riccardo and Visser, Otto and Marcos-Gragera, Rafael and Maynadi{\'e}, Marc and Simonetti, Arianna and Lutz, Jean-Michel and Berrino, Franco and {HAEMACARE Working Group}", affiliation = "Department of Preventive and Predictive Medicine, Unit of Analytical Epidemiology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. milena.sant@istitutotumori.mi.it", abstract = "Changing definitions and classifications of hematologic malignancies (HMs) complicate incidence comparisons. HAEMACARE classified HMs into groupings consistent with the latest World Health Organization classification and useful for epidemiologic and public health purposes. We present crude, age-specific and age-standardized incidence rates for European HMs according to these groupings, estimated from 66,371 lymphoid malignancies (LMs) and 21,796 myeloid malignancies (MMs) registered in 2000-2002 by 44 European cancer registries, grouped into 5 regions. Age-standardized incidence rates were 24.5 (per 100,000) for LMs and 7.55 for MMs. The commonest LMs were plasma cell neoplasms (4.62), small B-cell lymphocytic lymphoma/chronic lymphatic leukemia (3.79), diffuse B-cell lymphoma (3.13), and Hodgkin lymphoma (2.41). The commonest MMs were acute myeloid leukemia (2.96), other myeloproliferative neoplasms (1.76), and myelodysplastic syndrome (1.24). Unknown morphology LMs were commonest in Northern Europe (7.53); unknown morphology MMs were commonest in Southern Europe (0.73). Overall incidence was lowest in Eastern Europe and lower in women than in men. For most LMs, incidence was highest in Southern Europe; for MMs incidence was highest in the United Kingdom and Ireland. Differences in diagnostic and registration criteria are an important cause of incidence variation; however, different distribution of HM risk factors also contributes. The quality of population-based HM data needs further improvement.", journal = "Blood", volume = 116, number = 19, pages = "3724--3734", month = nov, year = 2010, language = "en" } @ARTICLE{Morton2006-zh, title = "Lymphoma incidence patterns by {WHO} subtype in the United States, 1992-2001", author = "Morton, Lindsay M and Wang, Sophia S and Devesa, Susan S and Hartge, Patricia and Weisenburger, Dennis D and Linet, Martha S", affiliation = "Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, 6120 Executive Blvd, EPS/7055, Rockville, MD 20852, USA. mortonli@mail.nih.gov", abstract = "Because the causes of most lymphoid neoplasms remain unknown, comparison of incidence patterns by disease subtype may provide critical clues for future etiologic investigations. We therefore conducted a comprehensive assessment of 114,548 lymphoid neoplasms diagnosed during 1992-2001 in 12 Surveillance, Epidemiology, and End Results (SEER) registries according to the internationally recognized World Health Organization (WHO) lymphoma classification introduced in 2001. Cases coded in International Classification of Diseases for Oncology, Second Edition (ICD-O-2), were converted to ICD-O-3 for WHO subtype assignment. Age-specific and age-adjusted rates were compared by sex and race (white, black, Asian). Age-adjusted trends in incidence were estimated by sex and race using weighted least squares log-linear regression. Diverse incidence patterns and trends were observed by lymphoid neoplasm subtype and population. In the elderly (75 years or older), rates of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma increased 1.4\% and 1.8\% per year, respectively, whereas rates of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) declined 2.1\% per year. Although whites bear the highest incidence burden for most lymphoid neoplasm subtypes, most notably for hairy cell leukemia and follicular lymphoma, black predominance was observed for plasma cell and T-cell neoplasms. Asians have considerably lower rates than whites and blacks for CLL/SLL and Hodgkin lymphoma. We conclude that the striking differences in incidence patterns by histologic subtype strongly suggest that there is etiologic heterogeneity among lymphoid neoplasms and support the pursuit of epidemiologic analysis by subtype.", journal = "Blood", volume = 107, number = 1, pages = "265--276", month = jan, year = 2006, language = "en" } @ARTICLE{Nanbo2007-fh, title = "The coupling of synthesis and partitioning of {EBV's} plasmid replicon is revealed in live cells", author = "Nanbo, Asuka and Sugden, Arthur and Sugden, Bill", affiliation = "McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI 53706, USA.", abstract = "Epstein-Barr virus (EBV) is an exceptionally successful human viral pathogen maintained as a licensed, plasmid replicon in proliferating cells. We have measured the distributions of EBV-derived plasmids in single live cells throughout the cell cycle in the absence of selection and confirmed the measured rates of duplication and partitioning computationally and experimentally. These analyses have uncovered a striking, non-random partitioning for this minimalist plasmid replicon and revealed additional properties of it and its host cells: (1) 84\% of the plasmids duplicate during each S phase; (2) all duplicated plasmids are spatially colocalized as pairs, a positioning that is coupled to their non-random partitioning; (3) each clone of cells requires a certain threshold number of plasmids per cell for its optimal growth under selection; (4) defects in plasmid synthesis and partitioning are balanced to yield wide distributions of plasmids in clonal populations of cells for which the plasmids provide a selective advantage. These properties of its plasmid replicon underlie EBV's success as a human pathogen.", journal = "EMBO J.", volume = 26, number = 19, pages = "4252--4262", month = oct, year = 2007, language = "en" } @ARTICLE{Gromminger2012-xa, title = "Burkitt lymphoma: the role of {Epstein-Barr} virus revisited", author = "Gr{\"o}mminger, Sebastian and Mautner, Josef and Bornkamm, Georg W", affiliation = "Institute of Clinical Molecular Biology and Tumour Genetics, German Research Centre for Environmental Health, Helmholtz Zentrum M{\"u}nchen, Marchioninistrasse 25, Munich, Germany.", journal = "Br. J. Haematol.", volume = 156, number = 6, pages = "719--729", month = mar, year = 2012, language = "en" } @ARTICLE{Dalla-Favera1982-lp, title = "Human c-myc onc gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells", author = "Dalla-Favera, R and Bregni, M and Erikson, J and Patterson, D and Gallo, R C and Croce, C M", abstract = "Human sequences related to the transforming gene (v-myc) of avian myelocytomatosis virus (MC29) are represented by at least one gene and several related sequences that may represent pseudogenes. By using a DNA probe that is specific for the complete gene (c-myc), different somatic cell hybrids possessing varying numbers of human chromosomes were analyzed by the Southern blotting technique. The results indicate that the human c-myc gene is located on chromosome 8. The analysis of hybrids between rodent cells and human Burkitt lymphoma cells, which carry a reciprocal translocation between chromosomes 8 and 14, allowed the mapping of the human c-myc gene on region (q24 leads to qter) of chromosome 8. This chromosomal region is translocated to either human chromosome 2, 14, or 22 in Burkitt lymphoma cells.", journal = "Proc. Natl. Acad. Sci. U. S. A.", volume = 79, number = 24, pages = "7824--7827", month = dec, year = 1982, language = "en" } @ARTICLE{Taub1982-fa, title = "Translocation of the c-myc gene into the immunoglobulin heavy chain locus in human Burkitt lymphoma and murine plasmacytoma cells", author = "Taub, R and Kirsch, I and Morton, C and Lenoir, G and Swan, D and Tronick, S and Aaronson, S and Leder, P", abstract = "The consistent appearance of specific chromosomal translocations in human Burkitt lymphomas and murine plasmacytomas has suggested that these translocations might play a role in malignant transformation. Here we show that transformation of these cells is frequently accompanied by the somatic rearrangement of a cellular analogue of an avian retrovirus transforming gene, c-myc. Moreover, we map c-myc to human chromosome 8 band q24, the chromosomal segment involved in the reciprocal Burkitt translocations [t(8;14), t(8;22) and t(2;8)]. In two t(8;14) human Burkitt cell lines, c-myc appears to have been translocated directly into a DNA restriction fragment that also encodes the immunoglobulin mu chain gene. In the case of a specific cloned fragment of DNA derived from a mouse plasmacytoma, we demonstrate directly that c-myc has been translocated into the immunoglobulin alpha switch region. Our data provide a molecular basis for considering the role that specific translocations might play in malignant transformation.", journal = "Proc. Natl. Acad. Sci. U. S. A.", volume = 79, number = 24, pages = "7837--7841", month = dec, year = 1982, language = "en" } @ARTICLE{Magrath2012-xr, title = "Epidemiology: clues to the pathogenesis of Burkitt lymphoma", author = "Magrath, Ian", affiliation = "International Network for Cancer Treatment and Research, Rue Engeland 642, Brussels, Belgium. imagrath@inctr.be", abstract = "The two major epidemiological clues to the pathogenesis of Burkitt lymphoma (BL) are the geographical association with malaria--BL incidence relates to the malaria transmission rate--and early infection by Epstein-Barr virus (EBV). Both agents cause B cell hyperplasia, which is almost certainly an essential component of lymphomagenesis in BL. The critical event in lymphomagenesis is the creation of a MYC translocation, bringing the MYC gene into juxtaposition with immunoglobulin genes and causing its ectopic expression, thereby driving the proliferation of BL cells. It is highly likely that such translocations are mediated by the activation-induced cytidine deaminase (AID) gene, which is responsible for hypervariable region mutations as well as class switching. Stimulation of the Toll-like receptor 9 by malaria-associated agonists induces AID, providing a mechanism whereby malaria could directly influence BL pathogenesis. EBV-containing cells must reach the memory cell compartment in order to survive throughout the life of the individual, which probably requires traversal of the germinal centre. Normally, cells that do not produce high affinity antibodies do not survive this passage, and are induced to undergo apoptosis. EBV, however, prevents this, and in doing so may also enhance the likelihood of survival of rare translocation-containing cells.", journal = "Br. J. Haematol.", volume = 156, number = 6, pages = "744--756", month = mar, year = 2012, language = "en" } @ARTICLE{Stone1987-pt, title = "Definition of regions in human c-myc that are involved in transformation and nuclear localization", author = "Stone, J and de Lange, T and Ramsay, G and Jakobovits, E and Bishop, J M and Varmus, H and Lee, W", abstract = "To study the relationship between the primary structure of the c-myc protein and some of its functional properties, we made in-frame insertion and deletion mutants of the normal human c-myc coding domain that was expressed from a retroviral promoter-enhancer. We assessed the effects of these mutations on the ability of c-myc protein to cotransform normal rat embryo cells with a mutant ras gene, induce foci in a Rat-1-derived cell line (Rat-1a), and localize in nuclei. Using the cotransformation assay, we found two regions of the protein (amino acids 105 to 143 and 321 to 439) where integrity was critical: one region (amino acids 1 to 104) that tolerated insertion and small deletion mutations, but not large deletions, and another region (amino acids 144) to 320) that was largely dispensable. Comparison with regions that were important for transformation of Rat-1a cells revealed that some are essential for both activities, but others are important for only one or the other, suggesting that the two assays require different properties of the c-myc protein. Deletion of each of three regions of the c-myc protein (amino acids 106 to 143, 320 to 368, and 370 to 412) resulted in partial cytoplasmic localization, as determined by immunofluorescence or immunoprecipitation following subcellular fractionation. Some abnormally located proteins retained transforming activity; most proteins lacking transforming activity appeared to be normally located.", journal = "Mol. Cell. Biol.", volume = 7, number = 5, pages = "1697--1709", month = may, year = 1987, language = "en" } @ARTICLE{Golub1999-qz, title = "Molecular classification of cancer: class discovery and class prediction by gene expression monitoring", author = "Golub, T R and Slonim, D K and Tamayo, P and Huard, C and Gaasenbeek, M and Mesirov, J P and Coller, H and Loh, M L and Downing, J R and Caligiuri, M A and Bloomfield, C D and Lander, E S", affiliation = "Whitehead Institute/Massachusetts Institute of Technology Center for Genome Research, Cambridge, MA 02139, USA. golub@genome.wi.mit.edu", abstract = "Although cancer classification has improved over the past 30 years, there has been no general approach for identifying new cancer classes (class discovery) or for assigning tumors to known classes (class prediction). Here, a generic approach to cancer classification based on gene expression monitoring by DNA microarrays is described and applied to human acute leukemias as a test case. A class discovery procedure automatically discovered the distinction between acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) without previous knowledge of these classes. An automatically derived class predictor was able to determine the class of new leukemia cases. The results demonstrate the feasibility of cancer classification based solely on gene expression monitoring and suggest a general strategy for discovering and predicting cancer classes for other types of cancer, independent of previous biological knowledge.", journal = "Science", volume = 286, number = 5439, pages = "531--537", month = oct, year = 1999, language = "en" } @ARTICLE{Guan2007-sk, title = "Amplification of {PVT1} contributes to the pathophysiology of ovarian and breast cancer", author = "Guan, Yinghui and Kuo, Wen-Lin and Stilwell, Jackie L and Takano, Hirokuni and Lapuk, Anna V and Fridlyand, Jane and Mao, Jian-Hua and Yu, Mamie and Miller, Melinda A and Santos, Jennifer L and Kalloger, Steve E and Carlson, Joseph W and Ginzinger, David G and Celniker, Susan E and Mills, Gordon B and Huntsman, David G and Gray, Joe W", affiliation = "Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.", abstract = "PURPOSE: This study was designed to elucidate the role of amplification at 8q24 in the pathophysiology of ovarian and breast cancer because increased copy number at this locus is one of the most frequent genomic abnormalities in these cancers. EXPERIMENTAL DESIGN: To accomplish this, we assessed the association of amplification at 8q24 with outcome in ovarian cancers using fluorescence in situ hybridization to tissue microarrays and measured responses of ovarian and breast cancer cell lines to specific small interfering RNAs against the oncogene MYC and a putative noncoding RNA, PVT1, both of which map to 8q24. RESULTS: Amplification of 8q24 was associated with significantly reduced survival duration. In addition, small interfering RNA-mediated reduction in either PVT1 or MYC expression inhibited proliferation in breast and ovarian cancer cell lines in which they were both amplified and overexpressed but not in lines in which they were not amplified/overexpressed. Inhibition of PVT1 expression also induced a strong apoptotic response in cell lines in which it was overexpressed but not in lines in which it was not amplified/overexpressed. Inhibition of MYC, on the other hand, did not induce an apoptotic response in cell lines in which MYC was amplified and overexpressed. CONCLUSIONS: These results suggest that MYC and PVT1 contribute independently to ovarian and breast pathogenesis when overexpressed because of genomic abnormalities. They also suggest that PVT1-mediated inhibition of apoptosis may explain why amplification of 8q24 is associated with reduced survival duration in patients treated with agents that act through apoptotic mechanisms.", journal = "Clin. Cancer Res.", volume = 13, number = 19, pages = "5745--5755", month = oct, year = 2007, language = "en" } @ARTICLE{Tseng2014-ol, title = "{PVT1} dependence in cancer with {MYC} copy-number increase", author = "Tseng, Yuen-Yi and Moriarity, Branden S and Gong, Wuming and Akiyama, Ryutaro and Tiwari, Ashutosh and Kawakami, Hiroko and Ronning, Peter and Reuland, Brian and Guenther, Kacey and Beadnell, Thomas C and Essig, Jaclyn and Otto, George M and O'Sullivan, M Gerard and Largaespada, David A and Schwertfeger, Kathryn L and Marahrens, York and Kawakami, Yasuhiko and Bagchi, Anindya", affiliation = "Department of Genetics, Cell Biology and Development, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA. 1] Masonic Cancer Center, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA [2]. 1] Department of Genetics, Cell Biology and Development, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA [2] Masonic Cancer Center, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA [3]. 1] Department of Genetics, Cell Biology and Development, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA [2] Stem Cell Institute, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA. 1] Masonic Cancer Center, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA [2] Center for Bio-Design, Translational Health Science and Technology Institute, Gurgaon 122016, India. Department of Laboratory Medicine and Pathology, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA. Masonic Cancer Center, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA. 1] Department of Genetics, Cell Biology and Development, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA [2] Masonic Cancer Center, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA. 1] Masonic Cancer Center, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA [2] Department of Laboratory Medicine and Pathology, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA [3]. 1] Department of Genetics, Cell Biology and Development, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA [2]. 1] Department of Genetics, Cell Biology and Development, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA [2] Stem Cell Institute, University of Minnesota, Twin Cities, Minneapolis, Minnesota 55455, USA [3].", abstract = "'Gain' of supernumerary copies of the 8q24.21 chromosomal region has been shown to be common in many human cancers and is associated with poor prognosis. The well-characterized myelocytomatosis (MYC) oncogene resides in the 8q24.21 region and is consistently co-gained with an adjacent 'gene desert' of approximately 2 megabases that contains the long non-coding RNA gene PVT1, the CCDC26 gene candidate and the GSDMC gene. Whether low copy-number gain of one or more of these genes drives neoplasia is not known. Here we use chromosome engineering in mice to show that a single extra copy of either the Myc gene or the region encompassing Pvt1, Ccdc26 and Gsdmc fails to advance cancer measurably, whereas a single supernumerary segment encompassing all four genes successfully promotes cancer. Gain of PVT1 long non-coding RNA expression was required for high MYC protein levels in 8q24-amplified human cancer cells. PVT1 RNA and MYC protein expression correlated in primary human tumours, and copy number of PVT1 was co-increased in more than 98\% of MYC-copy-increase cancers. Ablation of PVT1 from MYC-driven colon cancer line HCT116 diminished its tumorigenic potency. As MYC protein has been refractory to small-molecule inhibition, the dependence of high MYC protein levels on PVT1 long non-coding RNA provides a much needed therapeutic target.", journal = "Nature", volume = 512, number = 7512, pages = "82--86", month = aug, year = 2014, language = "en" } @ARTICLE{Carramusa2007-oc, title = "The {PVT-1} oncogene is a Myc protein target that is overexpressed in transformed cells", author = "Carramusa, Letizia and Contino, Flavia and Ferro, Arianna and Minafra, Luigi and Perconti, Giovanni and Giallongo, Agata and Feo, Salvatore", affiliation = "Dipartimento di Oncologia Sperimentale e Applicazioni Cliniche, Universit{\`a} di Palermo, Palermo, Italy.", abstract = "The human PVT-1 gene is located on chromosome 8 telomeric to the c-Myc gene and it is frequently involved in the translocations occurring in variant Burkitt's lymphomas and murine plasmacytomas. It has been proposed that PVT-1 regulates c-Myc gene transcription over a long distance. To get new insights into the functional relationships between the two genes, we have investigated PVT-1 and c-Myc expression in normal human tissues and in transformed cells. Our findings indicate that PVT-1 expression is restricted to a relative low number of normal tissues compared to the wide distribution of c-Myc mRNA, whereas the gene is highly expressed in many transformed cell types including neuroblastoma cells that do not express c-Myc. Reporter gene assays were used to dissect the PVT-1 promoter and to identify the region responsible for the elevated expression observed in transformed cells. This region contains two putative binding sites for Myc proteins. The results of transfection experiments in RAT1-MycER cells and chromatin immunoprecipitation (ChIP) assays in proliferating and differentiated neuroblastoma cells indicate that PVT-1 is a downstream target of Myc proteins.", journal = "J. Cell. Physiol.", volume = 213, number = 2, pages = "511--518", month = nov, year = 2007, language = "en" } @ARTICLE{Kwanhian2012-qb, title = "{MicroRNA-142} is mutated in about 20\% of diffuse large B-cell lymphoma", author = "Kwanhian, Wiyada and Lenze, Dido and Alles, Julia and Motsch, Natalie and Barth, Stephanie and D{\"o}ll, Celina and Imig, Jochen and Hummel, Michael and Tinguely, Marianne and Trivedi, Pankaj and Lulitanond, Viraphong and Meister, Gunter and Renner, Christoph and Gr{\"a}sser, Friedrich A", affiliation = "Institute of Virology, Saarland University Medical School 66421, Homburg, Germany; Department of Microbiology, Faculty of Medicine, Khon Kaen University 40002, Khon Kaen, Thailand.", abstract = "MicroRNAs (miRNAs) are short 18-23 nucleotide long noncoding RNAs that posttranscriptionally regulate gene expression by binding to mRNA. Our previous miRNA profiling of diffuse large B-cell lymphoma (DLBCL) revealed a mutation in the seed sequence of miR-142-3p. Further analysis now showed that miR-142 was mutated in 11 (19.64\%) of the 56 DLBCL cases. Of these, one case had a mutation in both alleles, with the remainder being heterozygous. Four mutations were found in the mature miR-142-5p, four in the mature miR-142-3p, and three mutations affected the miR-142 precursor. Two mutations in the seed sequence redirected miR-142-3p to the mRNA of the transcriptional repressor ZEB2 and one of them also targeted the ZEB1 mRNA. However, the other mutations in the mature miR-142-3p did not influence either the ZEB1 or ZEB2 3' untranslated region (3' UTR). On the other hand, the mutations affecting the seed sequence of miR-142-3p resulted in a loss of responsiveness in the 3' UTR of the known miR-142-3p targets RAC1 and ADCY9. In contrast to the mouse p300 gene, the human p300 gene was not found to be a target for miR-142-5p. In one case with a mutation of the precursor, we observed aberrant processing of the miR-142-5p. Our data suggest that the mutations in miR-142 probably lead to a loss rather than a gain of function. This is the first report describing mutations of a miRNA gene in a large percentage of a distinct lymphoma subtype.", journal = "Cancer Med.", volume = 1, number = 2, pages = "141--155", month = oct, year = 2012, keywords = "Carcinogenesis; cellular biology; genomics; molecular genetics", language = "en" } @ARTICLE{Hezaveh2016-pw, title = "Alterations of {microRNA} and {microRNA-regulated} messenger {RNA} expression in germinal center B-cell lymphomas determined by integrative sequencing analysis", author = "Hezaveh, Kebria and Kloetgen, Andreas and Bernhart, Stephan H and Mahapatra, Kunal Das and Lenze, Dido and Richter, Julia and Haake, Andrea and Bergmann, Anke K and Brors, Benedikt and Burkhardt, Birgit and Claviez, Alexander and Drexler, Hans G and Eils, Roland and Haas, Siegfried and Hoffmann, Steve and Karsch, Dennis and Klapper, Wolfram and Kleinheinz, Kortine and Korbel, Jan and Kretzmer, Helene and Kreuz, Markus and K{\"u}ppers, Ralf and Lawerenz, Chris and Leich, Ellen and Loeffler, Markus and Mantovani-Loeffler, Luisa and L{\'o}pez, Cristina and McHardy, Alice C and M{\"o}ller, Peter and Rohde, Marius and Rosenstiel, Philip and Rosenwald, Andreas and Schilhabel, Markus and Schlesner, Matthias and Scholz, Ingrid and Stadler, Peter F and Stilgenbauer, Stephan and Sungalee, St{\'e}phanie and Szczepanowski, Monika and Tr{\"u}mper, Lorenz and Weniger, Marc A and Siebert, Reiner and Borkhardt, Arndt and Hummel, Michael and Hoell, Jessica I and {ICGC MMML-Seq Project}", affiliation = "Department of Pediatric Oncology, Hematology and Clinical Immunology, Heinrich-Heine-University, Medical Faculty, D{\"u}sseldorf, Germany. Department of Algorithmic Bioinformatics, Heinrich-Heine University, Duesseldorf, Germany. Transcriptome Bioinformatics Group, LIFE Research Center for Civilization Diseases, University of Leipzig, Germany. Bioinformatics Group, Department of Computer Science, University of Leipzig, Germany. Interdisciplinary Center for Bioinformatics, University of Leipzig, Germany. Institute of Pathology, Charit{\'e} - University Medicine Berlin, Germany. Institute of Human Genetics, University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University Kiel, Germany. Division Applied Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany. National Center for Tumor Diseases (NCT), Heidelberg, Germany. German Cancer Consortium (DKTK), Heidelberg, Germany. Department of Pediatric Hematology and Oncology, University Hospital M{\"u}nster, Germany. Department of Pediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Germany. Department of Human and Animal Cell Cultures, German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany. Division of Theoretical Bioinformatics (B080), German Cancer Research Center (DKFZ), Heidelberg, Germany. Department of Bioinformatics and Functional Genomics, Institute for Pharmacy and Molecular Biotechnology and Bioquant, Heidelberg University, Germany. Friedrich-Ebert Hospital Neum{\"u}nster, Clinics for Hematology, Oncology and Nephrology, Neum{\"u}nster, Germany. Department of Internal Medicine II: Hematology and Oncology, University Medical Centre, Campus Kiel, Germany. Hematopathology Section, University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University Kiel, Germany. EMBL Heidelberg, Genome Biology, Heidelberg, Germany. Institute for Medical Informatics Statistics and Epidemiology, Leipzig, Germany. Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Essen, Germany. Institute of Pathology, University of W{\"u}rzburg, and Comprehensive Cancer Center Mainfranken, W{\"u}rzburg, Germany. Hospital of Internal Medicine II, Hematology and Oncology, St-Georg Hospital Leipzig, Germany. Computational Biology of Infection Research, Helmholtz Center for Infection Research, Braunschweig, Germany. Institute of Pathology, Medical Faculty of the Ulm University, Germany. Department of Pediatric Hematology and Oncology University Hospital Giessen, Germany. Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University Kiel, Germany. RNomics Group, Fraunhofer Institute for Cell Therapy and Immunology IZI, Leipzig, Germany. Max-Planck-Institute for Mathematics in Sciences, Leipzig, Germany. Santa Fe Institute, NM, USA. Department of Internal Medicine III, University of Ulm, Germany. Department of Hematology and Oncology, Georg-August-University of G{\"o}ttingen, Germany.", abstract = "MicroRNA are well-established players in post-transcriptional gene regulation. However, information on the effects of microRNA deregulation mainly relies on bioinformatic prediction of potential targets, whereas proof of the direct physical microRNA/target messenger RNA interaction is mostly lacking. Within the International Cancer Genome Consortium Project ``Determining Molecular Mechanisms in Malignant Lymphoma by Sequencing'', we performed miRnome sequencing from 16 Burkitt lymphomas, 19 diffuse large B-cell lymphomas, and 21 follicular lymphomas. Twenty-two miRNA separated Burkitt lymphomas from diffuse large B-cell lymphomas/follicular lymphomas, of which 13 have shown regulation by MYC. Moreover, we found expression of three hitherto unreported microRNA. Additionally, we detected recurrent mutations of hsa-miR-142 in diffuse large B-cell lymphomas and follicular lymphomas, and editing of the hsa-miR-376 cluster, providing evidence for microRNA editing in lymphomagenesis. To interrogate the direct physical interactions of microRNA with messenger RNA, we performed Argonaute-2 photoactivatable ribonucleoside-enhanced cross-linking and immunoprecipitation experiments. MicroRNA directly targeted 208 messsenger RNA in the Burkitt lymphomas and 328 messenger RNA in the non-Burkitt lymphoma models. This integrative analysis discovered several regulatory pathways of relevance in lymphomagenesis including Ras, PI3K-Akt and MAPK signaling pathways, also recurrently deregulated in lymphomas by mutations. Our dataset reveals that messenger RNA deregulation through microRNA is a highly relevant mechanism in lymphomagenesis.", journal = "Haematologica", volume = 101, number = 11, pages = "1380--1389", month = nov, year = 2016, language = "en" } @ARTICLE{Cerami2012-yj, title = "The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data", author = "Cerami, Ethan and Gao, Jianjiong and Dogrusoz, Ugur and Gross, Benjamin E and Sumer, Selcuk Onur and Aksoy, B{\"u}lent Arman and Jacobsen, Anders and Byrne, Caitlin J and Heuer, Michael L and Larsson, Erik and Antipin, Yevgeniy and Reva, Boris and Goldberg, Arthur P and Sander, Chris and Schultz, Nikolaus", affiliation = "Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. cancergenomics@cbio.mskcc.org", abstract = "The cBio Cancer Genomics Portal (http://cbioportal.org) is an open-access resource for interactive exploration of multidimensional cancer genomics data sets, currently providing access to data from more than 5,000 tumor samples from 20 cancer studies. The cBio Cancer Genomics Portal significantly lowers the barriers between complex genomic data and cancer researchers who want rapid, intuitive, and high-quality access to molecular profiles and clinical attributes from large-scale cancer genomics projects and empowers researchers to translate these rich data sets into biologic insights and clinical applications.", journal = "Cancer Discov.", volume = 2, number = 5, pages = "401--404", month = may, year = 2012, language = "en" } @ARTICLE{Gao2013-kj, title = "Integrative analysis of complex cancer genomics and clinical profiles using the {cBioPortal}", author = "Gao, Jianjiong and Aksoy, B{\"u}lent Arman and Dogrusoz, Ugur and Dresdner, Gideon and Gross, Benjamin and Sumer, S Onur and Sun, Yichao and Jacobsen, Anders and Sinha, Rileen and Larsson, Erik and Cerami, Ethan and Sander, Chris and Schultz, Nikolaus", affiliation = "Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.", abstract = "The cBioPortal for Cancer Genomics (http://cbioportal.org) provides a Web resource for exploring, visualizing, and analyzing multidimensional cancer genomics data. The portal reduces molecular profiling data from cancer tissues and cell lines into readily understandable genetic, epigenetic, gene expression, and proteomic events. The query interface combined with customized data storage enables researchers to interactively explore genetic alterations across samples, genes, and pathways and, when available in the underlying data, to link these to clinical outcomes. The portal provides graphical summaries of gene-level data from multiple platforms, network visualization and analysis, survival analysis, patient-centric queries, and software programmatic access. The intuitive Web interface of the portal makes complex cancer genomics profiles accessible to researchers and clinicians without requiring bioinformatics expertise, thus facilitating biological discoveries. Here, we provide a practical guide to the analysis and visualization features of the cBioPortal for Cancer Genomics.", journal = "Sci. Signal.", volume = 6, number = 269, pages = "l1", month = apr, year = 2013, language = "en" } @ARTICLE{Andersson2014-ri, title = "An atlas of active enhancers across human cell types and tissues", author = "Andersson, Robin and Gebhard, Claudia and Miguel-Escalada, Irene and Hoof, Ilka and Bornholdt, Jette and Boyd, Mette and Chen, Yun and Zhao, Xiaobei and Schmidl, Christian and Suzuki, Takahiro and Ntini, Evgenia and Arner, Erik and Valen, Eivind and Li, Kang and Schwarzfischer, Lucia and Glatz, Dagmar and Raithel, Johanna and Lilje, Berit and Rapin, Nicolas and Bagger, Frederik Otzen and J{\o}rgensen, Mette and Andersen, Peter Refsing and Bertin, Nicolas and Rackham, Owen and Burroughs, A Maxwell and Baillie, J Kenneth and Ishizu, Yuri and Shimizu, Yuri and Furuhata, Erina and Maeda, Shiori and Negishi, Yutaka and Mungall, Christopher J and Meehan, Terrence F and Lassmann, Timo and Itoh, Masayoshi and Kawaji, Hideya and Kondo, Naoto and Kawai, Jun and Lennartsson, Andreas and Daub, Carsten O and Heutink, Peter and Hume, David A and Jensen, Torben Heick and Suzuki, Harukazu and Hayashizaki, Yoshihide and M{\"u}ller, Ferenc and Forrest, Alistair R R and Carninci, Piero and Rehli, Michael and Sandelin, Albin", affiliation = "The Bioinformatics Centre, Department of Biology \& Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5, DK-2200 Copenhagen, Denmark. Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany. School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA. RIKEN OMICS Science Centre, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa, 230-0045, Japan. RIKEN Center for Life Science Technologies (Division of Genomic Technologies), RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa, 230-0045, Japan. Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology and Genetics, C.F. M{\o}llers Alle 3, Bldg. 1130, DK-8000 Aarhus, Denmark. Department of Molecular and Cellular Biology, Harvard University, USA. The Finsen Laboratory, Rigshospitalet and Danish Stem Cell Centre (DanStem), University of Copenhagen, Ole Maaloes Vej 5, DK-2200, Denmark. Roslin Institute, Edinburgh University, Easter Bush, Midlothian, EH25 9RG Scotland, UK. Genomics Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road MS 64-121, Berkeley, CA 94720, USA. EMBL Outstation - Hinxton, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD. RIKEN Preventive Medicine and Diagnosis Innovation Program, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa, 230-0045, Japan. Department of Biosciences and Nutrition, Karolinska Institutet, 14183 Huddinge, Stockholm, Sweden. Department of Clinical Genetics, VU University Medical Center, van der Boechorststraat 7, 1081 BT Amsterdam, Netherlands.", abstract = "Enhancers control the correct temporal and cell-type-specific activation of gene expression in multicellular eukaryotes. Knowing their properties, regulatory activity and targets is crucial to understand the regulation of differentiation and homeostasis. Here we use the FANTOM5 panel of samples, covering the majority of human tissues and cell types, to produce an atlas of active, in vivo-transcribed enhancers. We show that enhancers share properties with CpG-poor messenger RNA promoters but produce bidirectional, exosome-sensitive, relatively short unspliced RNAs, the generation of which is strongly related to enhancer activity. The atlas is used to compare regulatory programs between different cells at unprecedented depth, to identify disease-associated regulatory single nucleotide polymorphisms, and to classify cell-type-specific and ubiquitous enhancers. We further explore the utility of enhancer redundancy, which explains gene expression strength rather than expression patterns. The online FANTOM5 enhancer atlas represents a unique resource for studies on cell-type-specific enhancers and gene regulation.", journal = "Nature", volume = 507, number = 7493, pages = "455--461", month = mar, year = 2014, language = "en" } @ARTICLE{Wei2006-qw, title = "A global map of p53 transcription-factor binding sites in the human genome", author = "Wei, Chia-Lin and Wu, Qiang and Vega, Vinsensius B and Chiu, Kuo Ping and Ng, Patrick and Zhang, Tao and Shahab, Atif and Yong, How Choong and Fu, Yutao and Weng, Zhiping and Liu, Jianjun and Zhao, Xiao Dong and Chew, Joon-Lin and Lee, Yen Ling and Kuznetsov, Vladimir A and Sung, Wing-Kin and Miller, Lance D and Lim, Bing and Liu, Edison T and Yu, Qiang and Ng, Huck-Hui and Ruan, Yijun", affiliation = "Genome Institute of Singapore, Singapore 138672.", abstract = "The ability to derive a whole-genome map of transcription-factor binding sites (TFBS) is crucial for elucidating gene regulatory networks. Herein, we describe a robust approach that couples chromatin immunoprecipitation (ChIP) with the paired-end ditag (PET) sequencing strategy for unbiased and precise global localization of TFBS. We have applied this strategy to map p53 targets in the human genome. From a saturated sampling of over half a million PET sequences, we characterized 65,572 unique p53 ChIP DNA fragments and established overlapping PET clusters as a readout to define p53 binding loci with remarkable specificity. Based on this information, we refined the consensus p53 binding motif, identified at least 542 binding loci with high confidence, discovered 98 previously unidentified p53 target genes that were implicated in novel aspects of p53 functions, and showed their clinical relevance to p53-dependent tumorigenesis in primary cancer samples.", journal = "Cell", volume = 124, number = 1, pages = "207--219", month = jan, year = 2006, language = "en" } @ARTICLE{Bao2017-tn, title = "p53 binding sites in normal and cancer cells are characterized by distinct chromatin context", author = "Bao, Feifei and LoVerso, Peter R and Fisk, Jeffrey N and Zhurkin, Victor B and Cui, Feng", affiliation = "a Thomas H. Gosnell School of Life Sciences , Rochester Institute of Technology , Rochester , NY , USA. b Laboratory of Cell Biology , National Cancer Institute , Bethesda , MD , USA.", abstract = "The tumor suppressor protein p53 interacts with DNA in a sequence-dependent manner. Thousands of p53 binding sites have been mapped genome-wide in normal and cancer cells. However, the way p53 selectively binds its cognate sites in different types of cells is not fully understood. Here, we performed a comprehensive analysis of 25 published p53 cistromes and identified 3,551 and 6,039 'high-confidence' binding sites in normal and cancer cells, respectively. Our analysis revealed 2 distinct epigenetic features underlying p53-DNA interactions in vivo. First, p53 binding sites are associated with transcriptionally active histone marks (H3K4me3 and H3K36me3) in normal-cell chromatin, but with repressive histone marks (H3K27me3) in cancer-cell chromatin. Second, p53 binding sites in cancer cells are characterized by a lower level of DNA methylation than their counterparts in normal cells, probably related to global hypomethylation in cancers. Intriguingly, regardless of the cell type, p53 sites are highly enriched in the endogenous retroviral elements of the ERV1 family, highlighting the importance of this repeat family in shaping the transcriptional network of p53. Moreover, the p53 sites exhibit an unusual combination of chromatin patterns: high nucleosome occupancy and, at the same time, high sensitivity to DNase I. Our results suggest that p53 can access its target sites in a chromatin environment that is non-permissive to most DNA-binding transcription factors, which may allow p53 to act as a pioneer transcription factor in the context of chromatin.", journal = "Cell Cycle", volume = 16, number = 21, pages = "2073--2085", month = sep, year = 2017, keywords = "binding sites; chromatin; epigenetic features; p53; pioneer factors", language = "en" } @ARTICLE{Grygalewicz2017-cq, title = "The {11q-Gain/Loss} Aberration Occurs Recurrently in {MYC-Negative} Burkitt-like Lymphoma With 11q Aberration, as Well as {MYC-Positive} Burkitt Lymphoma and {MYC-Positive} {High-Grade} {B-Cell} Lymphoma, {NOS}", author = "Grygalewicz, Beata and Woroniecka, Renata and Rymkiewicz, Grzegorz and Rygier, Jolanta and Borkowska, Klaudia and Kotyl, Aleksandra and Blachnio, Katarzyna and Bystydzienski, Zbigniew and Nowakowska, Beata and Pienkowska-Grela, Barbara", affiliation = "Cytogenetic Laboratory, Maria Sklodowska-Curie Institute Oncology Center, Warsaw, Poland. Flow Cytometry Laboratory, Pathology and Laboratory Diagnostics Department, Maria Sklodowska-Curie Institute Oncology Center, Warsaw, Poland. Department of Medical Genetics, Mother and Child Institute, Warsaw, Poland.", abstract = "Objectives: The latest revision of lymphoma's World Health Organization classification describes the new provisional entity ``Burkitt-like lymphoma with 11q aberration'' (BLL, 11q) as lacking MYC rearrangement, but harboring the specific11q-gain/loss aberration. We report genetic characteristics of 11 lymphoma cases with this aberration. Methods: Classical cytogenetics, fluorescence in situ hybridization (FISH), and single nucleotide polymorphism/array comparative genomic hybridization. Results: The 11q aberrations were described as duplication, inversion, and deletion. Array comparative genomic hybridization showed two types of duplication: bigger than 50 megabase pairs (Mbp) and smaller than 20 Mbp, which were associated with bulky tumor larger than 20 cm and amplification of the 11q23.3 region, including KMT2A. Six cases revealed a normal FISH status of MYC and were diagnosed as BLL,11q. Five cases showed MYC rearrangement and were diagnosed as Burkitt lymphoma (BL) or high-grade B-cell lymphoma, not otherwise specified (HGBL, NOS). Conclusions: The 11q-gain/loss is not specific for BLL, 11q, but occurs recurrently in MYC-positive BL and MYC-positive HGBL.", journal = "Am. J. Clin. Pathol.", volume = 149, number = 1, pages = "17--28", month = dec, year = 2017, keywords = "11q-gain/loss; Burkitt-like lymphoma with 11q aberration; High-grade B-cell lymphoma; KMT2A; MYC", language = "en" } @ARTICLE{Rymkiewicz2018-zf, title = "A comprehensive flow-cytometry-based immunophenotypic characterization of Burkitt-like lymphoma with 11q aberration", author = "Rymkiewicz, Grzegorz and Grygalewicz, Beata and Chechlinska, Magdalena and Blachnio, Katarzyna and Bystydzienski, Zbigniew and Romejko-Jarosinska, Joanna and Woroniecka, Renata and Zajdel, Michalina and Domanska-Czyz, Katarzyna and Martin-Garcia, David and Nadeu, Ferran and Swoboda, Pawel and Rygier, Jolanta and Pienkowska-Grela, Barbara and Siwicki, Jan Konrad and Prochorec-Sobieszek, Monika and Salaverria, Itziar and Siebert, Reiner and Walewski, Jan", affiliation = "Flow Cytometry Laboratory, Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Institute-Oncology Center, Warsaw, Poland. Pathology Laboratory, Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Institute-Oncology Center, Warsaw, Poland. Cytogenetics Laboratory, Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Institute-Oncology Center, Warsaw, Poland. Department of Immunology, Maria Sklodowska-Curie Institute-Oncology Center, Warsaw, Poland. Department of Lymphoid Malignancies, Maria Sklodowska-Curie Institute-Oncology Center, Warsaw, Poland. Hematopathology Unit, Hospital Cl{\'\i}nic, Institut d'Investigacions Biom{\`e}diques August Pi i Sunyer (IDIBAPS), CIBERONC, University of Barcelona, Barcelona, Spain. Institute of Human Genetics, University Ulm and Ulm University Medical Center, Ulm, Germany.", abstract = "We previously described a subset of MYC translocation-negative aggressive B-cell lymphomas resembling Burkitt lymphoma, characterized by proximal gains and distal losses in chromosome 11. In the 2016 WHO classification, these MYC-negative lymphomas were recognized as a new provisional entity, 'Burkitt-like lymphoma with 11q aberration'. Here we present an immunophenotype analysis of Burkitt-like lymphomas with 11q aberration. Cells were acquired by fine needle aspiration biopsy from 10 young adult patients, 80\% of whom presented recurrence-free 5-year survival. Twenty-three MYC-positive Burkitt lymphomas, including three carrying both MYC rearrangement and 11q aberration, served as controls. By immunohistochemistry, all Burkitt-like lymphomas with 11q aberration were CD20+/CD10+/BCL6+/BCL2-/MUM1-/MYC+/EBV-, usually LMO2+/CD44-/CD43- and sometimes CD56+, and showed high proliferation rate. By flow cytometry, Burkitt-like lymphoma with 11q aberration immunophenotypically resembled MYC-positive Burkitt lymphoma, except for significantly (adjusted P<0.001) more frequent CD38higher expression in Burkitt lymphoma (91\% MYC-positive Burkitt lymphoma vs 10\% Burkitt-like lymphoma with 11q aberration), more frequently diminished CD45 expression in Burkitt lymphoma (74\% vs 10\%), an exclusive CD16/CD56 and highly restricted CD8 expression in Burkitt-like lymphoma with 11q aberration (60\% vs 0\% and 40\% vs 4\%, respectively). We showed high diagnostic accuracy and effectiveness of flow cytometry in Burkitt lymphoma. CD16/CD56 expression without CD38higher and the lack of CD16/CD56 with CD38higher expression proves to be a reliable, fast, and cost-effective method for diagnosing 11q aberration and MYC rearrangements in CD10(+) aggressive lymphomas, respectively. In addition, we confirmed a pattern of an inverted duplication with telomeric loss of 11q, as a recurrent 11q abnormality, but one case presented alternative changes, possibly resulting in an equivalent molecular effect. Our findings reveal similarities along with subtle but essential differences in the immunophenotype of Burkitt-like lymphoma with 11q aberration and MYC-positive Burkitt lymphoma, important for the differential diagnosis, but also for understanding the pathogenesis of Burkitt-like lymphoma with 11q aberration.Modern Pathology advance online publication, 12 January 2018; doi:10.1038/modpathol.2017.186.", journal = "Mod. Pathol.", month = jan, year = 2018, language = "en" } @ARTICLE{Kostareli2009-wi, title = "Molecular evidence for {EBV} and {CMV} persistence in a subset of patients with chronic lymphocytic leukemia expressing stereotyped {IGHV4-34} B-cell receptors", author = "Kostareli, E and Hadzidimitriou, A and Stavroyianni, N and Darzentas, N and Athanasiadou, A and Gounari, M and Bikos, V and Agathagelidis, A and Touloumenidou, T and Zorbas, I and Kouvatsi, A and Laoutaris, N and Fassas, A and Anagnostopoulos, A and Belessi, C and Stamatopoulos, K", affiliation = "School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece.", abstract = "The chronic lymphocytic leukemia (CLL) immunoglobulin repertoire is uniquely characterized by the presence of stereotyped B-cell receptors (BCRs). A major BCR stereotype in CLL is shared by immunoglobulin G-switched cases utilizing the immunoglobulin heavy-chain variable 4-34 (IGHV4-34) gene. Increased titers of IGHV4-34 antibodies are detected in selective clinical conditions, including infection by B-cell lymphotropic viruses, particularly Epstein-Barr virus (EBV) and cytomegalovirus (CMV). In this context, we sought evidence for persistent activation by EBV and CMV in CLL cases expressing the IGHV4-34 gene. The study group included 93 CLL cases with an intentional bias for the IGHV4-34 gene. On the basis of real-time PCR results for CMV/EBV DNA, cases were assigned to three groups: (1) double-negative (59/93); (2) single-positive (CMV- or EBV-positive; 25/93); (3) double-positive (9/93). The double-negative group was characterized by heterogeneous IGHV gene repertoire. In contrast, a bias for the IGHV4-34 gene was observed in the single-positive group (9/25 cases; 36\%). Remarkably, all nine double-positive cases utilized the IGHV4-34 gene; seven of nine cases expressed the major BCR stereotype as described above. In conclusion, our findings indicate that the interactions of CLL progenitor cells expressing distinctive IGHV4-34 BCRs with viral antigens/superantigens might facilitate clonal expansion and, eventually, leukemic transformation. The exact type, timing and location of these interactions remain to be determined.", journal = "Leukemia", volume = 23, number = 5, pages = "919--924", month = may, year = 2009, language = "en" } @ARTICLE{Kostareli2012-pf, title = "Antigen receptor stereotypy across B-cell lymphoproliferations: the case of {IGHV4-59/IGKV3-20} receptors with rheumatoid factor activity", author = "Kostareli, E and Gounari, M and Janus, A and Murray, F and Brochet, X and Giudicelli, V and Pospisilova, S and Oscier, D and Foroni, L and di Celle, P F and Tichy, B and Pedersen, L B and Jurlander, J and Ponzoni, M and Kouvatsi, A and Anagnostopoulos, A and Thompson, K and Darzentas, N and Lefranc, M-P and Belessi, C and Rosenquist, R and Davi, F and Ghia, P and Stamatopoulos, K", journal = "Leukemia", volume = 26, number = 5, pages = "1127--1131", month = may, year = 2012, language = "en" } @ARTICLE{Amato2016-jf, title = "Clonality Analysis of Immunoglobulin Gene Rearrangement by {Next-Generation} Sequencing in Endemic Burkitt Lymphoma Suggests Antigen Drive Activation of {BCR} as Opposed to Sporadic Burkitt Lymphoma", author = "Amato, Teresa and Abate, Francesco and Piccaluga, Pierpaolo and Iacono, Michele and Fallerini, Chiara and Renieri, Alessandra and De Falco, Giulia and Ambrosio, Maria Raffaella and Mourmouras, Vaselious and Ogwang, Martin and Calbi, Valeria and Rabadan, Roul and Hummel, Michael and Pileri, Stefano and Leoncini, Lorenzo and Bellan, Cristiana", affiliation = "From the Department of Medical Biotechnologies, University of Siena, Siena, Italy. Department of Biomedical Informatics, Columbia University College of Physicians and Surgeons, New York, NY. Hematopathology Section, Department of Experimental, Diagnostic, and Experimental Medicine (DIMES), S. Orsola-Malpighi Hospital, Bologna University School of Medicine, Bologna, Italy. Roche Tissue Diagnostic \& Sequencing, Roche Diagnostic S.P.A. Monza (MB), Italy. Lacor Hospital, Gulu, Uganda. Institut Fur Pathologie, Campus Benjamin Franklin, Charit{\`e}, Universitatsmedizin, Berlin, Germany. From the Department of Medical Biotechnologies, University of Siena, Siena, Italy lorenzo.leoncini@dbm.unisi.it.", abstract = "OBJECTIVES: Recent studies using next-generation sequencing (NGS) analysis disclosed the importance of the intrinsic activation of the B-cell receptor (BCR) pathway in the pathogenesis of sporadic Burkitt lymphoma (sBL) due to mutations of TCF3/ID3 genes. Since no definitive data are available on the genetic landscape of endemic Burkitt (eBL), we first assessed the mutation frequency of TCF3/ID3 in eBL compared with sBL and subsequently the somatic hypermutation status of the BCR to answer whether an extrinsic activation of BCR signaling could also be demonstrated in Burkitt lymphoma. METHODS: We assessed the mutations of TCF3/ID3 by RNAseq and the BCR status by NGS analysis of the immunoglobulin genes (IGs). RESULTS: We detected mutations of TCF3/ID3 in about 30\% of the eBL cases. This rate is significantly lower than that detected in sBL (64\%). The NGS analysis of IGs revealed intraclonal diversity, suggesting an active targeted somatic hypermutation process in eBL compared with sBL. CONCLUSIONS: These findings support the view that the antigenic pressure plays a key role in the pathogenetic pathways of eBL, which may be partially distinct from those driving sBL development.", journal = "Am. J. Clin. Pathol.", volume = 145, number = 1, pages = "116--127", month = jan, year = 2016, keywords = "BCR; Burkitt lymphoma; Clonality analysis; NGS", language = "en" } @ARTICLE{Baptista2014-sh, title = "Analysis of the {IGHV} region in Burkitt's lymphomas supports a germinal center origin and a role for superantigens in lymphomagenesis", author = "Baptista, Maria Joao and Calpe, Eva and Fernandez, Eva and Colomo, Lluis and Cardesa-Salzmann, Teresa Marta and Abrisqueta, Pau and Bosch, Francesc and Crespo, Marta", affiliation = "Laboratory of Experimental Hematology, Department of Hematology, Vall d'Hebron University Hospital, Universitat Auton{\`o}ma de Barcelona, Barcelona, Spain. Department of Pathology, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain. Department of Pediatric Oncology, Hospital Sant Joan de D{\'e}u, University of Barcelona, Barcelona, Spain. Laboratory of Experimental Hematology, Department of Hematology, Vall d'Hebron University Hospital, Universitat Auton{\`o}ma de Barcelona, Barcelona, Spain. Electronic address: fbosch@vhebron.net.", abstract = "The analysis of immunoglobulin heavy chain variable (IGHV) region may disclose the influence of antigens in Burkitt's lymphomas (BL). IGHV sequences from 38 patients and 35 cell lines were analyzed. IGHV3 subset genes were the most used and IGHV4-34 gene was overrepresented. IGHV genes were mutated in 98.6\% of the cases, 36\% acquired potential glycosylation sites, and in 52\% somatic-hypermutation-process was ongoing. Binding motifs for superantigens like Staphylococcal protein A and carbohydrate I/i were preserved in 89\% of the cases. IGHV analysis of BL cells supports a germinal center origin and points toward a role for superantigens in lymphomagenesis.", journal = "Leuk. Res.", volume = 38, number = 4, pages = "509--515", month = apr, year = 2014, keywords = "BL; Glycosylation; IGHV; Intraclonal diversity; SHM; Superantigens", language = "en" } @ARTICLE{Lombardo2017-dq, title = "High-throughput sequencing of the B-cell receptor in African Burkitt lymphoma reveals clues to pathogenesis", author = "Lombardo, Katharine A and Coffey, David G and Morales, Alicia J and Carlson, Christopher S and Towlerton, Andrea M H and Gerdts, Sarah E and Nkrumah, Francis K and Neequaye, Janet and Biggar, Robert J and Orem, Jackson and Casper, Corey and Mbulaiteye, Sam M and Bhatia, Kishor G and Warren, Edus H", affiliation = "Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA. Molecular and Cellular Biology Program and. Department of Medicine, School of Medicine, University of Washington, Seattle, WA. Division of Public Health Sciences and. Division of Vaccine and Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, WA. Noguchi Institute for Medical Research and. Department of Child Health, Medical School, University of Ghana, Accra, Ghana. Institute of Health and Biotechnical Innovation, Queensland University of Technology, Brisbane, QLD, Australia. Uganda Cancer Institute, Kampala, Uganda. Department of Global Health, School of Medicine, and. Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA; and. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.", abstract = "Burkitt lymphoma (BL), the most common pediatric cancer in sub-Saharan Africa, is a malignancy of antigen-experienced B lymphocytes. High-throughput sequencing (HTS) of the immunoglobulin heavy (IGH) and light chain (IGK/IGL) loci was performed on genomic DNA from 51 primary BL tumors: 19 from Uganda and 32 from Ghana. Reverse transcription polymerase chain reaction analysis and tumor RNA sequencing (RNAseq) was performed on the Ugandan tumors to confirm and extend the findings from the HTS of tumor DNA. Clonal IGH and IGK/IGL rearrangements were identified in 41 and 46 tumors, respectively. Evidence for rearrangement of the second IGH allele was observed in only 6 of 41 tumor samples with a clonal IGH rearrangement, suggesting that the normal process of biallelic IGHD to IGHJ diversity-joining (DJ) rearrangement is often disrupted in BL progenitor cells. Most tumors, including those with a sole dominant, nonexpressed DJ rearrangement, contained many IGH and IGK/IGL sequences that differed from the dominant rearrangement by < 10 nucleotides, suggesting that the target of ongoing mutagenesis of these loci in BL tumor cells is not limited to expressed alleles. IGHV usage in both BL tumor cohorts revealed enrichment for IGHV genes that are infrequently used in memory B cells from healthy subjects. Analysis of publicly available DNA sequencing and RNAseq data revealed that these same IGHV genes were overrepresented in dominant tumor-associated IGH rearrangements in several independent BL tumor cohorts. These data suggest that BL derives from an abnormal B-cell progenitor and that aberrant mutational processes are active on the immunoglobulin loci in BL cells.", journal = "Blood Adv", volume = 1, number = 9, pages = "535--544", month = mar, year = 2017, language = "en" } @ARTICLE{Bolotin2017-hm, title = "Antigen receptor repertoire profiling from {RNA-seq} data", author = "Bolotin, Dmitriy A and Poslavsky, Stanislav and Davydov, Alexey N and Frenkel, Felix E and Fanchi, Lorenzo and Zolotareva, Olga I and Hemmers, Saskia and Putintseva, Ekaterina V and Obraztsova, Anna S and Shugay, Mikhail and Ataullakhanov, Ravshan I and Rudensky, Alexander Y and Schumacher, Ton N and Chudakov, Dmitriy M", affiliation = "MiLaboratory LLC, Skolkovo Innovation Center, Moscow, Russia. Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia. Pirogov Russian National Research Medical University, Moscow, Russia. Central European Institute of Technology, Brno, Czech Republic. BostonGene LLC, Lincoln, Massachusetts, USA. Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. Howard Hughes Medical Institute and Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. Centre for Genomic Regulation, The Barcelona Institute for Science and Technology, Barcelona, Spain. Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia. Nizhny Novgorod State Medical Academy, Nizhny Novgorod, Russia. Center for Data-Intensive Biomedicine and Biotechnology, Skolkovo Institute of Science and Technology, Moscow, Russia. Institute of Immunology FMBA, Moscow, Russia. Faculties for Physics and Biology, Lomonosov Moscow State University, Moscow, Russia. Ludwig Center at Memorial Sloan Kettering Cancer Center, Memorial Sloan Kettering Cancer Center, New York, New York, USA.", journal = "Nat. Biotechnol.", volume = 35, number = 10, pages = "908--911", month = oct, year = 2017, language = "en" } @ARTICLE{Bolotin2015-az, title = "{MiXCR}: software for comprehensive adaptive immunity profiling", author = "Bolotin, Dmitriy A and Poslavsky, Stanislav and Mitrophanov, Igor and Shugay, Mikhail and Mamedov, Ilgar Z and Putintseva, Ekaterina V and Chudakov, Dmitriy M", affiliation = "1] Shemyakin-Ovchinnikov Institute of bioorganic chemistry RAS, Moscow, Russia. [2] Pirogov Russian National Research Medical University, Moscow, Russia. Shemyakin-Ovchinnikov Institute of bioorganic chemistry RAS, Moscow, Russia. 1] Shemyakin-Ovchinnikov Institute of bioorganic chemistry RAS, Moscow, Russia. [2] Pirogov Russian National Research Medical University, Moscow, Russia. [3] Central European Institute of Technology, Masaryk University, Brno, Czech Republic.", journal = "Nat. Methods", volume = 12, number = 5, pages = "380--381", month = may, year = 2015, language = "en" } @BOOK{Swerdlow2017-rn, title = "{WHO} Classification of Tumours of Haematopoietic and Lymphoid Tissues ({IARC} {WHO} Classification of Tumours)", author = "Swerdlow, S and Campo, E and Harris, N L and Jaffe, E S and Pileri, S A and Stein, H and Thiele, J and Arber, D and Hasserjian, R and Le Beau, M", publisher = "World Health Organization", edition = "Revised edition", month = sep, year = 2017, language = "en" } @ARTICLE{Sandlund2006-tm, title = "A subtle t(3;8) results in plausible juxtaposition of {MYC} and {BCL6} in a child with Burkitt lymphoma/leukemia and ataxia-telangiectasia", author = "Sandlund, John T and Kastan, Michael B and Kennedy, Wren and Behm, Frederick and Entrekin, Elaine and Pui, Ching-Hon and Kalwinsky, David T and Raimondi, Susana C", affiliation = "Department of Hematology/Oncology, St. Jude Children's Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105, USA. john.sandlund@stjude.org", abstract = "Translocations involving 3q27 that affect the BCL6 gene are common and specific chromosomal abnormalities in B-cell precursor non-Hodgkin lymphoma (mainly diffuse large-cell and follicular lymphoma), but they have not been reported in Burkitt lymphoma. Here, we describe a case in which a BCL6 rearrangement and additional complex cytogenetic abnormalities occurred in a child with Burkitt lymphoma/leukemia and ataxia-telangiectasia. Although cytogenetic analysis of the bone marrow revealed clonal abnormalities of chromosome arms 8q and 14p and other subclonal abnormalities, the t(8;14) or its variants typically associated with Burkitt lymphoma were not observed. Fluorescence in situ hybridization with locus-specific probes and multicolor spectral karyotyping demonstrated a complex pattern of chromosomal rearrangements leading to a subtle t(3;8)(q27;q24.1) that rearranged BCL6 and placed it adjacent to MYC. We speculate that this genetic lesion occurred as a result of chromosomal instability due to the underlying disease.", journal = "Cancer Genet. Cytogenet.", volume = 168, number = 1, pages = "69--72", month = jul, year = 2006, language = "en" } @ARTICLE{Wang2007-lf, title = "A novel t(3;8)(q27;q24.1) simultaneously involving both the {BCL6} and {MYC} genes in a diffuse large B-cell lymphoma", author = "Wang, Huan-You and Bossler, Aaron D and Schaffer, Andras and Tomczak, Ewa and DiPatri, Doris and Frank, Dale M and Nowell, Peter C and Bagg, Adam", affiliation = "Department of Pathology and Laboratory Medicine, School of Medicine, Hospital of the University of Pennsylvania, 7.103 Founders Pavilion, 3400 Spruce Street, Philadelphia, PA 19014-4284, USA.", abstract = "Diffuse large B-cell lymphomas (DLBCLs) are a clinically and biologically heterogeneous group of hematologic malignancies. Specific genetic aberrations underlie some of this heterogeneity. These genetic events include distinct and separate translocations resulting in the dysregulated expression of either BCL6 protein with the t(3;14)(q27;q32) or c-MYC protein with the t(8;14)(q24;q32), as a consequence of the juxtaposition of these oncogenes with heterologous promoters or enhancers, such as those of the immunoglobulin heavy chain gene. Here, we report the case of a patient with DLBCL with a unique t(3;8)(q27;q24.1) that involves the BCL6 and MYC genes. We know of no previous report of this translocation in DLBCL, which simultaneously affects two key genes implicated in lymphomagenesis and may reflect a novel genetic mechanism in neoplastic transformation.", journal = "Cancer Genet. Cytogenet.", volume = 172, number = 1, pages = "45--53", month = jan, year = 2007, language = "en" } @ARTICLE{Bertrand2007-nx, title = "Mapping of {MYC} breakpoints in 8q24 rearrangements involving non-immunoglobulin partners in B-cell lymphomas", author = "Bertrand, P and Bastard, C and Maingonnat, C and Jardin, F and Maisonneuve, C and Courel, M-N and Ruminy, P and Picquenot, J-M and Tilly, H", affiliation = "Groupe d'Etude des Prolif{\'e}rations Lympho{\"\i}des, Centre Henri Becquerel, INSERM U614, IFRMP23, Rouen, France. pbertrand@rouen.fnclcc.fr", abstract = "Chromosomal translocations joining the immunoglobulin (IG) and MYC genes have been extensively reported in Burkitt's and non-Burkitt's lymphomas but data concerning MYC rearrangements with non-IG partners are scarce. In this study, 8q24 breakpoints from 17 B-cell lymphomas involving non-IG loci were mapped by fluorescence in situ hybridization (FISH). In seven cases the breakpoint was inside a small region encompassing MYC: in one t(7;8)(p12;q24) and two t(3;8)(q27;q24), it was telomeric to MYC whereas in four cases, one t(2;8)(p15;q24) and three t(8;9)(q24;p13) it was located in a 85 kb region encompassing MYC. In these seven cases, partner regions identified by FISH contained genes known to be involved in lymphomagenesis, namely BCL6, BCL11A, PAX5 and IKAROS. Breakpoints were cloned in two t(8;9)(q24;p13), 2.5 and 7 kb downstream from MYC and several hundred kb 5' to PAX5 on chromosome 9, joining MYC to ZCCHC7 and to ZBTB5 exon 2, two genes encoding zinc-finger proteins. In these seven cases, MYC expression measured by quantitative reverse transcription-polymerase chain reaction (RT-PCR) was significantly higher when compared to that of patients without 8q24 rearrangement (P=0.006). These results suggest that these rearrangements are the consequence of a non-random process targeting MYC together with non-IG genes involved in lymphocyte differentiation and lymphoma progression.", journal = "Leukemia", volume = 21, number = 3, pages = "515--523", month = mar, year = 2007, language = "en" } @ARTICLE{Huret2009-lo, title = "t(3;8)(q27;q24)", author = "Huret, J L", abstract = "Review on t(3;8)(q27;q24), with data on clinics, and the genes involved.", publisher = "Jean-Loup Huret (Editor-in-Chief) ; INIST-CNRS (Publisher)", year = 2009, keywords = "Chromosome 3; Chromosome 8; Article", language = "en" } @ARTICLE{Puente2015-gx, title = "Non-coding recurrent mutations in chronic lymphocytic leukaemia", author = "Puente, Xose S and Be{\`a}, Silvia and Vald{\'e}s-Mas, Rafael and Villamor, Neus and Guti{\'e}rrez-Abril, Jes{\'u}s and Mart{\'\i}n-Subero, Jos{\'e} I and Munar, Marta and Rubio-P{\'e}rez, Carlota and Jares, Pedro and Aymerich, Marta and Baumann, Tycho and Beekman, Ren{\'e}e and Belver, Laura and Carrio, Anna and Castellano, Giancarlo and Clot, Guillem and Colado, Enrique and Colomer, Dolors and Costa, Dolors and Delgado, Julio and Enjuanes, Anna and Estivill, Xavier and Ferrando, Adolfo A and Gelp{\'\i}, Josep L and Gonz{\'a}lez, Blanca and Gonz{\'a}lez, Santiago and Gonz{\'a}lez, Marcos and Gut, Marta and Hern{\'a}ndez-Rivas, Jes{\'u}s M and L{\'o}pez-Guerra, M{\'o}nica and Mart{\'\i}n-Garc{\'\i}a, David and Navarro, Alba and Nicol{\'a}s, Pilar and Orozco, Modesto and Payer, {\'A}ngel R and Pinyol, Magda and Pisano, David G and Puente, Diana A and Queir{\'o}s, Ana C and Quesada, V{\'\i}ctor and Romeo-Casabona, Carlos M and Royo, Cristina and Royo, Romina and Rozman, Mar{\'\i}a and Russi{\~n}ol, Nuria and Salaverr{\'\i}a, Itziar and Stamatopoulos, Kostas and Stunnenberg, Hendrik G and Tamborero, David and Terol, Mar{\'\i}a J and Valencia, Alfonso and L{\'o}pez-Bigas, Nuria and Torrents, David and Gut, Ivo and L{\'o}pez-Guillermo, Armando and L{\'o}pez-Ot{\'\i}n, Carlos and Campo, El{\'\i}as", affiliation = "Departamento de Bioqu{\'\i}mica y Biolog{\'\i}a Molecular, Instituto Universitario de Oncolog{\'\i}a (IUOPA), Universidad de Oviedo, 33006 Oviedo, Spain. Institut d'Investigacions Biom{\`e}diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain. Unitat de Hematolog{\'\i}a, Hospital Cl{\'\i}nic, IDIBAPS, Universitat de Barcelona, 08036 Barcelona, Spain. Departament d'Anatom{\'\i}a Patol{\`o}gica, Microbiolog{\'\i}a i Farmacolog{\'\i}a, Universitat de Barcelona, 08036 Barcelona, Spain. Programa Conjunto de Biolog{\'\i}a Computacional, Barcelona Supercomputing Center (BSC), Institut de Recerca Biom{\`e}dica (IRB), Spanish National Bioinformatics Institute, Universitat de Barcelona, 08028 Barcelona, Spain. Research Unit on Biomedical Informatics, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain. Unidad de Gen{\'o}mica, IDIBAPS, 08036 Barcelona, Spain. Servicio de Hematolog{\'\i}a, Hospital Cl{\'\i}nic, IDIBAPS, 08036 Barcelona, Spain. Institute for Cancer Genetics, Columbia University, New York 10032, USA. Servicio de Hematolog{\'\i}a, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain. Center for Genomic Regulation (CRG), Pompeu Fabra University (UPF), Hospital del Mar Research Institute (IMIM), 08003 Barcelona, Spain. Servicio de Hematolog{\'\i}a, IBSAL-Hospital Universitario de Salamanca, Centro de Investigaci{\'o}n del C{\'a}ncer, Universidad de Salamanca-CSIC, 37007 Salamanca, Spain. Centro Nacional de An{\'a}lisis Gen{\'o}mico, Parc Cient{\'\i}fic de Barcelona, 08028 Barcelona, Spain. C{\'a}tedra Inter-Universitaria de Derecho y Genoma Humano, Universidad de Deusto, Universidad del Pa{\'\i}s Vasco, 48007 Bilbao, Spain. Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre (CNIO), Spanish National Bioinformatics Institute, 28029 Madrid, Spain. Institute of Applied Biosciences, Center for Research and Technology Hellas, 57001 Thermi, Thessaloniki, Greece. Department of Molecular Biology, Faculty of Science, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen, 6500 HB Nijmegen, The Netherlands. Servicio de Hematolog{\'\i}a, Hospital Cl{\'\i}nico de Valencia, 46010 Valencia, Spain.", abstract = "Chronic lymphocytic leukaemia (CLL) is a frequent disease in which the genetic alterations determining the clinicobiological behaviour are not fully understood. Here we describe a comprehensive evaluation of the genomic landscape of 452 CLL cases and 54 patients with monoclonal B-lymphocytosis, a precursor disorder. We extend the number of CLL driver alterations, including changes in ZNF292, ZMYM3, ARID1A and PTPN11. We also identify novel recurrent mutations in non-coding regions, including the 3' region of NOTCH1, which cause aberrant splicing events, increase NOTCH1 activity and result in a more aggressive disease. In addition, mutations in an enhancer located on chromosome 9p13 result in reduced expression of the B-cell-specific transcription factor PAX5. The accumulative number of driver alterations (0 to $\geq$4) discriminated between patients with differences in clinical behaviour. This study provides an integrated portrait of the CLL genomic landscape, identifies new recurrent driver mutations of the disease, and suggests clinical interventions that may improve the management of this neoplasia.", journal = "Nature", volume = 526, number = 7574, pages = "519--524", month = oct, year = 2015, language = "en" } @ARTICLE{Kalchschmidt2016-je, title = "{Epstein-Barr} virus nuclear protein {EBNA3C} directly induces expression of {AID} and somatic mutations in {B} cells", author = "Kalchschmidt, Jens S and Bashford-Rogers, Rachael and Paschos, Kostas and Gillman, Adam C T and Styles, Christine T and Kellam, Paul and Allday, Martin J", affiliation = "Molecular Virology, Department of Medicine, Imperial College London, London W2 1PG, England, UK. Wellcome Trust Sanger Institute, Cambridge CB10 1SA, England, UK. Molecular Virology, Department of Medicine, Imperial College London, London W2 1PG, England, UK m.allday@imperial.ac.uk.", abstract = "Activation-induced cytidine deaminase (AID), the enzyme responsible for induction of sequence variation in immunoglobulins (Igs) during the process of somatic hypermutation (SHM) and also Ig class switching, can have a potent mutator phenotype in the development of lymphoma. Using various Epstein-Barr virus (EBV) recombinants, we provide definitive evidence that the viral nuclear protein EBNA3C is essential in EBV-infected primary B cells for the induction of AID mRNA and protein. Using lymphoblastoid cell lines (LCLs) established with EBV recombinants conditional for EBNA3C function, this was confirmed, and it was shown that transactivation of the AID gene (AICDA) is associated with EBNA3C binding to highly conserved regulatory elements located proximal to and upstream of the AICDA transcription start site. EBNA3C binding initiated epigenetic changes to chromatin at specific sites across the AICDA locus. Deep sequencing of cDNA corresponding to the IgH V-D-J region from the conditional LCL was used to formally show that SHM is activated by functional EBNA3C and induction of AID. These data, showing the direct targeting and induction of functional AID by EBNA3C, suggest a novel role for EBV in the etiology of B cell cancers, including endemic Burkitt lymphoma.", journal = "J. Exp. Med.", volume = 213, number = 6, pages = "921--928", month = may, year = 2016, language = "en" } @ARTICLE{Dave2006-pq, title = "Molecular diagnosis of Burkitt's lymphoma", author = "Dave, Sandeep S and Fu, Kai and Wright, George W and Lam, Lloyd T and Kluin, Philip and Boerma, Evert-Jan and Greiner, Timothy C and Weisenburger, Dennis D and Rosenwald, Andreas and Ott, German and M{\"u}ller-Hermelink, Hans-Konrad and Gascoyne, Randy D and Delabie, Jan and Rimsza, Lisa M and Braziel, Rita M and Grogan, Thomas M and Campo, Elias and Jaffe, Elaine S and Dave, Bhavana J and Sanger, Warren and Bast, Martin and Vose, Julie M and Armitage, James O and Connors, Joseph M and Smeland, Erlend B and Kvaloy, Stein and Holte, Harald and Fisher, Richard I and Miller, Thomas P and Montserrat, Emilio and Wilson, Wyndham H and Bahl, Manisha and Zhao, Hong and Yang, Liming and Powell, John and Simon, Richard and Chan, Wing C and Staudt, Louis M and {Lymphoma/Leukemia Molecular Profiling Project}", affiliation = "National Cancer Institute, National Institutes of Health, Bethesda, Md, USA.", abstract = "BACKGROUND: The distinction between Burkitt's lymphoma and diffuse large-B-cell lymphoma is crucial because these two types of lymphoma require different treatments. We examined whether gene-expression profiling could reliably distinguish Burkitt's lymphoma from diffuse large-B-cell lymphoma. METHODS: Tumor-biopsy specimens from 303 patients with aggressive lymphomas were profiled for gene expression and were also classified according to morphology, immunohistochemistry, and detection of the t(8;14) c-myc translocation. RESULTS: A classifier based on gene expression correctly identified all 25 pathologically verified cases of classic Burkitt's lymphoma. Burkitt's lymphoma was readily distinguished from diffuse large-B-cell lymphoma by the high level of expression of c-myc target genes, the expression of a subgroup of germinal-center B-cell genes, and the low level of expression of major-histocompatibility-complex class I genes and nuclear factor-kappaB target genes. Eight specimens with a pathological diagnosis of diffuse large-B-cell lymphoma had the typical gene-expression profile of Burkitt's lymphoma, suggesting they represent cases of Burkitt's lymphoma that are difficult to diagnose by current methods. Among 28 of the patients with a molecular diagnosis of Burkitt's lymphoma, the overall survival was superior among those who had received intensive chemotherapy regimens instead of lower-dose regimens. CONCLUSIONS: Gene-expression profiling is an accurate, quantitative method for distinguishing Burkitt's lymphoma from diffuse large-B-cell lymphoma.", journal = "N. Engl. J. Med.", volume = 354, number = 23, pages = "2431--2442", month = jun, year = 2006, language = "en" } @ARTICLE{Caron2009-nf, title = "{CXCR4} expression functionally discriminates centroblasts versus centrocytes within human germinal center {B} cells", author = "Caron, Gersende and Le Gallou, Simon and Lamy, Thierry and Tarte, Karin and Fest, Thierry", affiliation = "Unit{\'e} 917, Facult{\'e} de M{\'e}decine, Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale, Universit{\'e} Rennes 1, Rennes, France.", abstract = "The human germinal center is a highly dynamic structure where B cells conduct their terminal differentiation and traffic following chemokine gradients. The rapidly dividing centroblasts and the nondividing centrocytes represent the two major B cell subsets present in germinal center and also the most common normal counterparts for a majority of lymphomas. CD77 expression was previously associated to proliferating centroblasts undergoing somatic hypermutation, but data from transcriptional studies demonstrate that CD77 is not a reliable marker to discriminate human centroblasts from centrocytes. Herein we were able for the first time to separate these two subpopulations based on the expression of the chemokine receptor CXCR4 allowing their characterization. Phenotypic and functional features were especially explored, giving an accurate definition of CXCR4(+) centroblasts compared with CXCR4(-) centrocytes. We show that CXCR4(+) and CXCR4(-) germinal center B cells present a clear dichotomy in terms of proliferation, transcription factor expression, Ig production, and somatic hypermutation regulation. Microarray analysis identified an extensive gene list segregating these B cells, including highly relevant genes according to previous knowledge. By gene set enrichment analysis we demonstrated that the centroblastic gene expression signature was significantly enriched in Burkitt's lymphomas. Collectively, our findings show that CXCR4 expression can properly separate human centroblasts from centrocytes and offer now the possibility to have purified normal counterparts of mature B cell-derived malignancies.", journal = "J. Immunol.", volume = 182, number = 12, pages = "7595--7602", month = jun, year = 2009, language = "en" } % The entry below contains non-ASCII chars that could not be converted % to a LaTeX equivalent. @UNPUBLISHED{Arthur2017-kj, title = "Genome-wide discovery of somatic coding and regulatory variants in Diffuse Large B-cell Lymphoma", author = "Arthur, Sarah and Jiang, Aixiang and Grande, Bruno and Alcaide, Miguel and Mottok, Anja and Ennishi, Daisuke and Rushton, Christopher and Jessa, Selin and Lat, Prince Kumar and Pararajalingam, Prasath and Meissner, Barbara and Boyle, Merrill and Chong, Lauren and Lai, Daniel and Farinha, Pedro and Slack, Graham and Davidson, Jordan and Bushell, Kevin and Shah, Sohrab and Sen, Dipankar and Jones, Steven and Mungall, Andrew J and Gascoyne, Randy and Marra, Marco A and Steidl, Christian and Connors, Joseph and Scott, David and Morin, Ryan D", abstract = "Diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer originating from mature B-cells. Many known driver mutations are over-represented in one of its two molecular subgroups, knowledge of which has aided in the development of therapeutics that target these features. The heterogeneity of DLBCL determined through prior genomic analysis suggests an incomplete understanding of its molecular aetiology, with a limited diversity of genetic events having thus far been attributed to the activated B-cell (ABC) subgroup. Through an integrative genomic analysis we uncovered genes and non-coding loci that are commonly mutated in DLBCL including putative regulatory sequences. We implicate recurrent mutations in the 3′UTR of NFKBIZ as a novel mechanism of oncogene deregulation and found small amplifications associated with over-expression of FC-$\gamma$ receptor genes. These results inform on mechanisms of NF-$\kappa$B pathway activation in ABC DLBCL and may reveal a high-risk population of patients that might not benefit from standard therapeutics.", journal = "bioRxiv", pages = "225870", month = dec, year = 2017, language = "en" } @ARTICLE{Kaymaz2017-xm, title = "Comprehensive Transcriptome and Mutational Profiling of Endemic Burkitt Lymphoma Reveals {EBV} Type-specific Differences", author = "Kaymaz, Yasin and Oduor, Cliff I and Yu, Hongbo and Otieno, Juliana A and Ong'echa, John M and Moormann, Ann M and Bailey, Jeffrey A", affiliation = "Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School. Department of Biomedical Sciences and Technology, Maseno University. Department of Pathology, University of Massachusetts Medical School. Ministry of Health, Jaramogi Onginga Odinga Teaching and Referral Hospital. Center for Global Health Research, Kenya Medical Research Institute. Program in Molecular Medicine, University of Massachusetts Medical School. Division of Transfusion Medicine, Department of Medicine, University of Massachusetts Medical School jeffrey.bailey@umassmed.edu.", abstract = "Endemic Burkitt lymphoma (eBL) is the most common pediatric cancer in malaria-endemic equatorial Africa and nearly always contains Epstein-Barr virus (EBV), unlike sporadic Burkitt Lymphoma (sBL) that occurs with a lower incidence in developed countries. Given these differences and the variable clinical presentation and outcomes, we sought to further understand pathogenesis by investigating transcriptomes using RNA sequencing (RNAseq) from multiple primary eBL tumors compared to sBL tumors. Within eBL tumors, minimal expression differences were found based on: anatomical presentation site, in-hospital survival rates, and EBV genome type; suggesting that eBL tumors are homogeneous without marked subtypes. The outstanding difference detected using surrogate variable analysis was the significantly decreased expression of key genes in the immunoproteasome complex (PSMB9/beta1i, PSMB10/$\beta$2i, PSMB8/beta5i, and PSME2/PA28beta) in eBL tumors carrying type 2 EBV compared to type 1 EBV. Secondly, in comparison to previously published pediatric sBL specimens, the majority of the expression and pathway differences was related to the PTEN/PI3K/mTOR signaling pathway and was correlated most strongly with EBV status rather than geographic designation. Third, common mutations were observed significantly less frequently in eBL tumors harboring EBV type 1, with mutation frequencies similar between tumors with EBV type 2 and without EBV. In addition to the previously reported genes, a set of new genes mutated in BL including TFAP4, MSH6, PRRC2C, BCL7A, FOXO1, PLCG2, PRKDC, RAD50, and RPRD2 were identified. Overall, these data establish that EBV, particularly EBV type 1, supports BL oncogenesis alleviating the need for certain driver mutations in the human genome. IMPLICATIONS: Genomic and mutational analyses of Burkitt lymphoma tumors identify key differences based on viral content and clinical outcomes suggesting new avenues for the development of prognostic molecular biomarkers and therapeutic interventions.", journal = "Mol. Cancer Res.", month = jan, year = 2017, language = "en" } @ARTICLE{Li2002-rk, title = "Deubiquitination of p53 by {HAUSP} is an important pathway for p53 stabilization", author = "Li, Muyang and Chen, Delin and Shiloh, Ariel and Luo, Jianyuan and Nikolaev, Anatoly Y and Qin, Jun and Gu, Wei", affiliation = "Institute for Cancer Genetics, and Department of Pathology, College of Physicians \& Surgeons, Columbia University, 1150 St Nicholas Avenue, New York, New York 10032, USA.", abstract = "The p53 tumour suppressor is a short-lived protein that is maintained at low levels in normal cells by Mdm2-mediated ubiquitination and subsequent proteolysis. Stabilization of p53 is crucial for its tumour suppressor function. However, the precise mechanism by which ubiquitinated p53 levels are regulated in vivo is not completely understood. By mass spectrometry of affinity-purified p53-associated factors, we have identified herpesvirus-associated ubiquitin-specific protease (HAUSP) as a novel p53-interacting protein. HAUSP strongly stabilizes p53 even in the presence of excess Mdm2, and also induces p53-dependent cell growth repression and apoptosis. Significantly, HAUSP has an intrinsic enzymatic activity that specifically deubiquitinates p53 both in vitro and in vivo. In contrast, expression of a catalytically inactive point mutant of HAUSP in cells increases the levels of p53 ubiquitination and destabilizes p53. These findings reveal an important mechanism by which p53 can be stabilized by direct deubiquitination and also imply that HAUSP might function as a tumour suppressor in vivo through the stabilization of p53.", journal = "Nature", volume = 416, number = 6881, pages = "648--653", month = apr, year = 2002, language = "en" } @ARTICLE{Nascimento2011-xq, title = "The opposing transcriptional functions of Sin3a and c-Myc are required to maintain tissue homeostasis", author = "Nascimento, Elisabete M and Cox, Claire L and MacArthur, Stewart and Hussain, Shobbir and Trotter, Matthew and Blanco, Sandra and Suraj, Menon and Nichols, Jennifer and K{\"u}bler, Bernd and Benitah, Salvador Aznar and Hendrich, Brian and Odom, Duncan T and Frye, Michaela", affiliation = "Wellcome Trust Centre for Stem Cell Research, University of Cambridge, Cambridge CB2 1QR, UK.", abstract = "How the proto-oncogene c-Myc balances the processes of stem-cell self-renewal, proliferation and differentiation in adult tissues is largely unknown. We explored c-Myc's transcriptional roles at the epidermal differentiation complex, a locus essential for skin maturation. Binding of c-Myc can simultaneously recruit (Klf4, Ovol-1) and displace (Cebpa, Mxi1 and Sin3a) specific sets of differentiation-specific transcriptional regulators to epidermal differentiation complex genes. We found that Sin3a causes deacetylation of c-Myc protein to directly repress c-Myc activity. In the absence of Sin3a, genomic recruitment of c-Myc to the epidermal differentiation complex is enhanced, and re-activation of c-Myc-target genes drives aberrant epidermal proliferation and differentiation. Simultaneous deletion of c-Myc and Sin3a reverts the skin phenotype to normal. Our results identify how the balance of two transcriptional key regulators can maintain tissue homeostasis through a negative feedback loop.", journal = "Nat. Cell Biol.", volume = 13, number = 12, pages = "1395--1405", month = nov, year = 2011, language = "en" } @ARTICLE{Mularoni2016-ze, title = "{OncodriveFML}: a general framework to identify coding and non-coding regions with cancer driver mutations", author = "Mularoni, Loris and Sabarinathan, Radhakrishnan and Deu-Pons, Jordi and Gonzalez-Perez, Abel and L{\'o}pez-Bigas, N{\'u}ria", affiliation = "Research Program on Biomedical Informatics, IMIM Hospital del Mar Medical Research Institute and Universitat Pompeu Fabra, Doctor Aiguader 88, 08003, Barcelona, Catalonia, Spain. Research Program on Biomedical Informatics, IMIM Hospital del Mar Medical Research Institute and Universitat Pompeu Fabra, Doctor Aiguader 88, 08003, Barcelona, Catalonia, Spain. Research Program on Biomedical Informatics, IMIM Hospital del Mar Medical Research Institute and Universitat Pompeu Fabra, Doctor Aiguader 88, 08003, Barcelona, Catalonia, Spain. Research Program on Biomedical Informatics, IMIM Hospital del Mar Medical Research Institute and Universitat Pompeu Fabra, Doctor Aiguader 88, 08003, Barcelona, Catalonia, Spain. Research Program on Biomedical Informatics, IMIM Hospital del Mar Medical Research Institute and Universitat Pompeu Fabra, Doctor Aiguader 88, 08003, Barcelona, Catalonia, Spain. nuria.lopez@upf.edu. Instituci{\'o} Catalana de Recerca i Estudis Avan{\c c}ats (ICREA), Passeig Llu{\'\i}s Companys 23, 08010, Barcelona, Spain. nuria.lopez@upf.edu.", abstract = "Distinguishing the driver mutations from somatic mutations in a tumor genome is one of the major challenges of cancer research. This challenge is more acute and far from solved for non-coding mutations. Here we present OncodriveFML, a method designed to analyze the pattern of somatic mutations across tumors in both coding and non-coding genomic regions to identify signals of positive selection, and therefore, their involvement in tumorigenesis. We describe the method and illustrate its usefulness to identify protein-coding genes, promoters, untranslated regions, intronic splice regions, and lncRNAs-containing driver mutations in several malignancies.", journal = "Genome Biol.", volume = 17, number = 1, pages = "128", month = jun, year = 2016, keywords = "Cancer drivers; Local functional mutations bias; Non-coding drivers; Non-coding regions", language = "en" } @ARTICLE{Salaverria2014-up, title = "A recurrent 11q aberration pattern characterizes a subset of {MYC-negative} high-grade B-cell lymphomas resembling Burkitt lymphoma", author = "Salaverria, Itziar and Martin-Guerrero, Idoia and Wagener, Rabea and Kreuz, Markus and Kohler, Christian W and Richter, Julia and Pienkowska-Grela, Barbara and Adam, Patrick and Burkhardt, Birgit and Claviez, Alexander and Damm-Welk, Christine and Drexler, Hans G and Hummel, Michael and Jaffe, Elaine S and K{\"u}ppers, Ralf and Lefebvre, Christine and Lisfeld, Jasmin and L{\"o}ffler, Markus and Macleod, Roderick A F and Nagel, Inga and Oschlies, Ilske and Rosolowski, Maciej and Russell, Robert B and Rymkiewicz, Grzegorz and Schindler, Detlev and Schlesner, Matthias and Scholtysik, Ren{\'e} and Schwaenen, Carsten and Spang, Rainer and Szczepanowski, Monika and Tr{\"u}mper, Lorenz and Vater, Inga and Wessendorf, Swen and Klapper, Wolfram and Siebert, Reiner and {Molecular Mechanisms in Malignant Lymphoma Network Project} and {Berlin-Frankfurt-M{\"u}nster Non-Hodgkin Lymphoma Group}", affiliation = "Institute of Human Genetics, University Hospital Schleswig-Holstein, Campus Kiel/Christian-Albrechts University, Kiel, Germany;", abstract = "The genetic hallmark of Burkitt lymphoma (BL) is the t(8;14)(q24;q32) and its variants leading to activation of the MYC oncogene. It is a matter of debate whether true BL without MYC translocation exists. Here, we identified 59 lymphomas concordantly called BL by 2 gene expression classifiers among 753 B-cell lymphomas. Only 2 (3\%) of these 59 molecular BL lacked a MYC translocation, which both shared a peculiar pattern of chromosome 11q aberration characterized by interstitial gains including 11q23.2-q23.3 and telomeric losses of 11q24.1-qter. We extended our analysis to 17 MYC-negative high-grade B-cell lymphomas with a similar 11q aberration and showed this aberration to be recurrently associated with morphologic and clinical features of BL. The minimal region of gain was defined by high-level amplifications in 11q23.3 and associated with overexpression of genes including PAFAH1B2 on a transcriptional and protein level. The recurrent region of loss contained a focal homozygous deletion in 11q24.2-q24.3 including the ETS1 gene, which was shown to be mutated in 4 of 16 investigated cases. These findings indicate the existence of a molecularly distinct subset of B-cell lymphomas reminiscent of BL, which is characterized by deregulation of genes in 11q.", journal = "Blood", volume = 123, number = 8, pages = "1187--1198", month = feb, year = 2014, language = "en" } @ARTICLE{Tamborero2013-xi, title = "{OncodriveCLUST}: exploiting the positional clustering of somatic mutations to identify cancer genes", author = "Tamborero, David and Gonzalez-Perez, Abel and Lopez-Bigas, Nuria", affiliation = "Research Unit on Biomedical Informatics, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Dr. Aiguader 88, 08003 Barcelona and Instituci{\'o} Catalana de Recerca i Estudis Avan{\c c}ats ICREA, Passeig Lluis Companys, 23, 08010 Barcelona, Spain.", abstract = "MOTIVATION: Gain-of-function mutations often cluster in specific protein regions, a signal that those mutations provide an adaptive advantage to cancer cells and consequently are positively selected during clonal evolution of tumours. We sought to determine the overall extent of this feature in cancer and the possibility to use this feature to identify drivers. RESULTS: We have developed OncodriveCLUST, a method to identify genes with a significant bias towards mutation clustering within the protein sequence. This method constructs the background model by assessing coding-silent mutations, which are assumed not to be under positive selection and thus may reflect the baseline tendency of somatic mutations to be clustered. OncodriveCLUST analysis of the Catalogue of Somatic Mutations in Cancer retrieved a list of genes enriched by the Cancer Gene Census, prioritizing those with dominant phenotypes but also highlighting some recessive cancer genes, which showed wider but still delimited mutation clusters. Assessment of datasets from The Cancer Genome Atlas demonstrated that OncodriveCLUST selected cancer genes that were nevertheless missed by methods based on frequency and functional impact criteria. This stressed the benefit of combining approaches based on complementary principles to identify driver mutations. We propose OncodriveCLUST as an effective tool for that purpose. AVAILABILITY: OncodriveCLUST has been implemented as a Python script and is freely available from http://bg.upf.edu/oncodriveclust CONTACT: nuria.lopez@upf.edu or abel.gonzalez@upf.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.", journal = "Bioinformatics", volume = 29, number = 18, pages = "2238--2244", month = sep, year = 2013 } @ARTICLE{Lawrence2013-ph, title = "Mutational heterogeneity in cancer and the search for new cancer-associated genes", author = "Lawrence, Michael S and Stojanov, Petar and Polak, Paz and Kryukov, Gregory V and Cibulskis, Kristian and Sivachenko, Andrey and Carter, Scott L and Stewart, Chip and Mermel, Craig H and Roberts, Steven A and Kiezun, Adam and Hammerman, Peter S and McKenna, Aaron and Drier, Yotam and Zou, Lihua and Ramos, Alex H and Pugh, Trevor J and Stransky, Nicolas and Helman, Elena and Kim, Jaegil and Sougnez, Carrie and Ambrogio, Lauren and Nickerson, Elizabeth and Shefler, Erica and Cort{\'e}s, Maria L and Auclair, Daniel and Saksena, Gordon and Voet, Douglas and Noble, Michael and DiCara, Daniel and Lin, Pei and Lichtenstein, Lee and Heiman, David I and Fennell, Timothy and Imielinski, Marcin and Hernandez, Bryan and Hodis, Eran and Baca, Sylvan and Dulak, Austin M and Lohr, Jens and Landau, Dan-Avi and Wu, Catherine J and Melendez-Zajgla, Jorge and Hidalgo-Miranda, Alfredo and Koren, Amnon and McCarroll, Steven A and Mora, Jaume and Lee, Ryan S and Crompton, Brian and Onofrio, Robert and Parkin, Melissa and Winckler, Wendy and Ardlie, Kristin and Gabriel, Stacey B and Roberts, Charles W M and Biegel, Jaclyn A and Stegmaier, Kimberly and Bass, Adam J and Garraway, Levi A and Meyerson, Matthew and Golub, Todd R and Gordenin, Dmitry A and Sunyaev, Shamil and Lander, Eric S and Getz, Gad", affiliation = "The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02141, USA.", abstract = "Major international projects are underway that are aimed at creating a comprehensive catalogue of all the genes responsible for the initiation and progression of cancer. These studies involve the sequencing of matched tumour-normal samples followed by mathematical analysis to identify those genes in which mutations occur more frequently than expected by random chance. Here we describe a fundamental problem with cancer genome studies: as the sample size increases, the list of putatively significant genes produced by current analytical methods burgeons into the hundreds. The list includes many implausible genes (such as those encoding olfactory receptors and the muscle protein titin), suggesting extensive false-positive findings that overshadow true driver events. We show that this problem stems largely from mutational heterogeneity and provide a novel analytical methodology, MutSigCV, for resolving the problem. We apply MutSigCV to exome sequences from 3,083 tumour-normal pairs and discover extraordinary variation in mutation frequency and spectrum within cancer types, which sheds light on mutational processes and disease aetiology, and in mutation frequency across the genome, which is strongly correlated with DNA replication timing and also with transcriptional activity. By incorporating mutational heterogeneity into the analyses, MutSigCV is able to eliminate most of the apparent artefactual findings and enable the identification of genes truly associated with cancer.", journal = "Nature", volume = 499, number = 7457, pages = "214--218", month = jul, year = 2013 } @ARTICLE{Jacobson2014-am, title = "How {I} treat Burkitt lymphoma in adults", author = "Jacobson, Caron and LaCasce, Ann", affiliation = "Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.", abstract = "Burkitt lymphoma (BL) is an aggressive B-cell non-Hodgkin lymphoma that is almost uniformly associated with translocations involving the gene for MYC on chromosome 8. The 3 subtypes of BL, endemic, sporadic, and immunodeficiency-associated, differ from epidemiologic and clinical perspectives but may be genetically similar. Prompt administration of multiagent immunochemotherapy regimens is associated with favorable outcomes for the majority of patients. Survival is inferior in older patients, likely reflecting increased therapy-related toxicity, possibly resulting in decreased treatment intensity. Central nervous system prophylaxis, tumor lysis prevention and treatment, and management of infectious complications from myelosuppressive regimens are critical. Prognosis of refractory or relapsed disease is poor and patients are best treated on clinical trials when available.", journal = "Blood", volume = 124, number = 19, pages = "2913--2920", month = nov, year = 2014 } @ARTICLE{Schmitz2012-df, title = "Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics", author = "Schmitz, Roland and Young, Ryan M and Ceribelli, Michele and Jhavar, Sameer and Xiao, Wenming and Zhang, Meili and Wright, George W and Shaffer, Arthur L and Hodson, Daniel J and Buras, Eric and Liu, Xuelu and Powell, John and Yang, Yandan and Xu, Weihong and Zhao, Hong and Kohlhammer, Holger and Rosenwald, Andreas and Kluin, Philip and M{\"u}ller-Hermelink, Hans Konrad and Ott, German and Gascoyne, Randy D and Connors, Joseph M and Rimsza, Lisa M and Campo, Elias and Jaffe, Elaine S and Delabie, Jan and Smeland, Erlend B and Ogwang, Martin D and Reynolds, Steven J and Fisher, Richard I and Braziel, Rita M and Tubbs, Raymond R and Cook, James R and Weisenburger, Dennis D and Chan, Wing C and Pittaluga, Stefania and Wilson, Wyndham H and Waldmann, Thomas A and Rowe, Martin and Mbulaiteye, Sam M and Rickinson, Alan B and Staudt, Louis M", affiliation = "Metabolism Branch Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.", abstract = "Burkitt's lymphoma (BL) can often be cured by intensive chemotherapy, but the toxicity of such therapy precludes its use in the elderly and in patients with endemic BL in developing countries, necessitating new strategies. The normal germinal centre B cell is the presumed cell of origin for both BL and diffuse large B-cell lymphoma (DLBCL), yet gene expression analysis suggests that these malignancies may use different oncogenic pathways. BL is subdivided into a sporadic subtype that is diagnosed in developed countries, the Epstein-Barr-virus-associated endemic subtype, and an HIV-associated subtype, but it is unclear whether these subtypes use similar or divergent oncogenic mechanisms. Here we used high-throughput RNA sequencing and RNA interference screening to discover essential regulatory pathways in BL that cooperate with MYC, the defining oncogene of this cancer. In 70\% of sporadic BL cases, mutations affecting the transcription factor TCF3 (E2A) or its negative regulator ID3 fostered TCF3 dependency. TCF3 activated the pro-survival phosphatidylinositol-3-OH kinase pathway in BL, in part by augmenting tonic B-cell receptor signalling. In 38\% of sporadic BL cases, oncogenic CCND3 mutations produced highly stable cyclin D3 isoforms that drive cell cycle progression. These findings suggest opportunities to improve therapy for patients with BL.", journal = "Nature", publisher = "Nature Publishing Group", volume = 490, number = 7418, pages = "116--120", month = oct, year = 2012, keywords = "burkitt lymphoma; rna sequencing" } @ARTICLE{Victora2012-pa, title = "Identification of human germinal center light and dark zone cells and their relationship to human B-cell lymphomas", author = "Victora, Gabriel D and Dominguez-Sola, David and Holmes, Antony B and Deroubaix, Stephanie and Dalla-Favera, Riccardo and Nussenzweig, Michel C", affiliation = "Laboratory of Molecular Immunology, Rockefeller University, New York, NY, USA. victora@wi.mit.edu", abstract = "Germinal centers (GCs) are sites of B-cell clonal expansion, hypermutation, and selection. GCs are polarized into dark (DZ) and light zones (LZ), a distinction that is of key importance to GC selection. However, the difference between the B cells in each of these zones in humans remains unclear. We show that, as in mice, CXCR4 and CD83 can be used to distinguish human LZ and DZ cells. Using these markers, we show that LZ and DZ cells in mice and humans differ only in the expression of characteristic ``activation'' and ``proliferation'' programs, suggesting that these populations represent alternating states of a single-cell type rather than distinct differentiation stages. In addition, LZ/DZ transcriptional profiling shows that, with the exception of ``molecular'' Burkitt lymphomas, nearly all human B-cell malignancies closely resemble LZ cells, which has important implications for our understanding of the molecular programs of lymphomagenesis.", journal = "Blood", publisher = "American Society of Hematology", volume = 120, number = 11, pages = "2240--2248", month = sep, year = 2012, keywords = "burkitt lymphoma; gene expression microarray; non-hodgkin lymphoma" } @ARTICLE{Love2012-qk, title = "The genetic landscape of mutations in Burkitt lymphoma", author = "Love, Cassandra and Sun, Zhen and Jima, Dereje and Li, Guojie and Zhang, Jenny and Miles, Rodney and Richards, Kristy L and Dunphy, Cherie H and Choi, William W L and Srivastava, Gopesh and Lugar, Patricia L and Rizzieri, David A and Lagoo, Anand S and Bernal-Mizrachi, Leon and Mann, Karen P and Flowers, Christopher R and Naresh, Kikkeri N and Evens, Andrew M and Chadburn, Amy and Gordon, Leo I and Czader, Magdalena B and Gill, Javed I and Hsi, Eric D and Greenough, Adrienne and Moffitt, Andrea B and McKinney, Matthew and Banerjee, Anjishnu and Grubor, Vladimir and Levy, Shawn and Dunson, David B and Dave, Sandeep S", affiliation = "Duke Institute for Genome Sciences and Policy, Duke University, Durham, NC, USA.", abstract = "Burkitt lymphoma is characterized by deregulation of MYC, but the contribution of other genetic mutations to the disease is largely unknown. Here, we describe the first completely sequenced genome from a Burkitt lymphoma tumor and germline DNA from the same affected individual. We further sequenced the exomes of 59 Burkitt lymphoma tumors and compared them to sequenced exomes from 94 diffuse large B-cell lymphoma (DLBCL) tumors. We identified 70 genes that were recurrently mutated in Burkitt lymphomas, including ID3, GNA13, RET, PIK3R1 and the SWI/SNF genes ARID1A and SMARCA4. Our data implicate a number of genes in cancer for the first time, including CCT6B, SALL3, FTCD and PC. ID3 mutations occurred in 34\% of Burkitt lymphomas and not in DLBCLs. We show experimentally that ID3 mutations promote cell cycle progression and proliferation. Our work thus elucidates commonly occurring gene-coding mutations in Burkitt lymphoma and implicates ID3 as a new tumor suppressor gene.", journal = "Nat. Genet.", publisher = "Nature Publishing Group", volume = 44, number = 12, pages = "1321--1325", month = dec, year = 2012, keywords = "burkitt lymphoma; exome sequencing" } @ARTICLE{Richter2012-ay, title = "Recurrent mutation of the {ID3} gene in Burkitt lymphoma identified by integrated genome, exome and transcriptome sequencing", author = "Richter, Julia and Schlesner, Matthias and Hoffmann, Steve and Kreuz, Markus and Leich, Ellen and Burkhardt, Birgit and Rosolowski, Maciej and Ammerpohl, Ole and Wagener, Rabea and Bernhart, Stephan H and Lenze, Dido and Szczepanowski, Monika and Paulsen, Maren and Lipinski, Simone and Russell, Robert B and Adam-Klages, Sabine and Apic, Gordana and Claviez, Alexander and Hasenclever, Dirk and Hovestadt, Volker and Hornig, Nadine and Korbel, Jan O and Kube, Dieter and Langenberger, David and Lawerenz, Chris and Lisfeld, Jasmin and Meyer, Katharina and Picelli, Simone and Pischimarov, Jordan and Radlwimmer, Bernhard and Rausch, Tobias and Rohde, Marius and Schilhabel, Markus and Scholtysik, Ren{\'e} and Spang, Rainer and Trautmann, Heiko and Zenz, Thorsten and Borkhardt, Arndt and Drexler, Hans G and M{\"o}ller, Peter and MacLeod, Roderick A F and Pott, Christiane and Schreiber, Stefan and Tr{\"u}mper, Lorenz and Loeffler, Markus and Stadler, Peter F and Lichter, Peter and Eils, Roland and K{\"u}ppers, Ralf and Hummel, Michael and Klapper, Wolfram and Rosenstiel, Philip and Rosenwald, Andreas and Brors, Benedikt and Siebert, Reiner and {ICGC MMML-Seq Project}", affiliation = "Institute of Human Genetics, Christian-Albrechts-University, Kiel, Germany.", abstract = "Burkitt lymphoma is a mature aggressive B-cell lymphoma derived from germinal center B cells. Its cytogenetic hallmark is the Burkitt translocation t(8;14)(q24;q32) and its variants, which juxtapose the MYC oncogene with one of the three immunoglobulin loci. Consequently, MYC is deregulated, resulting in massive perturbation of gene expression. Nevertheless, MYC deregulation alone seems not to be sufficient to drive Burkitt lymphomagenesis. By whole-genome, whole-exome and transcriptome sequencing of four prototypical Burkitt lymphomas with immunoglobulin gene (IG)-MYC translocation, we identified seven recurrently mutated genes. One of these genes, ID3, mapped to a region of focal homozygous loss in Burkitt lymphoma. In an extended cohort, 36 of 53 molecularly defined Burkitt lymphomas (68\%) carried potentially damaging mutations of ID3. These were strongly enriched at somatic hypermutation motifs. Only 6 of 47 other B-cell lymphomas with the IG-MYC translocation (13\%) carried ID3 mutations. These findings suggest that cooperation between ID3 inactivation and IG-MYC translocation is a hallmark of Burkitt lymphomagenesis.", journal = "Nat. Genet.", publisher = "Nature Publishing Group", volume = 44, number = 12, pages = "1316--1320", month = dec, year = 2012, keywords = "bisulfite sequencing; burkitt lymphoma; exome sequencing; rna sequencing; whole genome sequencing" } @ARTICLE{Schmitz2014-tz, title = "Oncogenic mechanisms in Burkitt lymphoma", author = "Schmitz, Roland and Ceribelli, Michele and Pittaluga, Stefania and Wright, George W and Staudt, Louis M", affiliation = "Lymphoid Malignancies Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892.", abstract = "Burkitt lymphoma is a germinal center B-cell-derived cancer that was instrumental in the identification of MYC as an important human oncogene more than three decades ago. Recently, new genomics technologies have uncovered several additional oncogenic mechanisms that cooperate with MYC to create this highly aggressive cancer. The transcription factor TCF-3 is central to Burkitt lymphoma pathogenesis. TCF-3 is rendered constitutively active in Burkitt lymphoma by two related mechanisms: (1) somatic mutations that inactivate its negative regulator ID3, and (2) somatic mutations in TCF-3 that block the ability of ID3 to bind and interfere with its activity as a transcription factor. TCF-3 is also a master regulator of normal germinal center B-cell differentiation. Within the germinal center, TCF-3 up-regulates genes that are characteristically expressed in the rapidly dividing centroblasts, the putative cell of origin for Burkitt lymphoma, while repressing genes expressed in the less proliferative centrocytes. TCF-3 promotes antigen-independent (tonic) B-cell-receptor signaling in Burkitt lymphoma by transactivating immunoglobulin heavy- and light-chain genes while repressing PTPN6, which encodes the phosphatase SHP-1, a negative regulator of B-cell-receptor signaling. Tonic B-cell-receptor signaling sustains Burkitt lymphoma survival by engaging the PI3 kinase pathway. In addition, TCF-3 promotes cell-cycle progression by transactivating CCND3, encoding a D-type cyclin that regulates the G1-S phase transition. Additionally, CCND3 accumulates oncogenic mutations that stabilize cyclin D3 protein expression and drive proliferation. These new insights into Burkitt lymphoma pathogenesis suggest new therapeutic strategies, which are sorely needed in developing regions of the world where this cancer is endemic.", journal = "Cold Spring Harb. Perspect. Med.", volume = 4, number = 2, pages = "a014282--a014282", month = feb, year = 2014, keywords = "burkitt lymphoma; review" } @ARTICLE{Abate2015-iu, title = "Distinct Viral and Mutational Spectrum of Endemic Burkitt Lymphoma", author = "Abate, Francesco and Ambrosio, Maria Raffaella and Mundo, Lucia and Laginestra, Maria Antonella and Fuligni, Fabio and Rossi, Maura and Zairis, Sakellarios and Gazaneo, Sara and De Falco, Giulia and Lazzi, Stefano and Bellan, Cristiana and Rocca, Bruno Jim and Amato, Teresa and Marasco, Elena and Etebari, Maryam and Ogwang, Martin and Calbi, Valeria and Ndede, Isaac and Patel, Kirtika and Chumba, David and Piccaluga, Pier Paolo and Pileri, Stefano and Leoncini, Lorenzo and Rabadan, Raul", affiliation = "Department of Systems Biology, Columbia University College of Physicians and Surgeons, New York, New York, United States of America; Department of Biomedical Informatics, Columbia University College of Physicians and Surgeons, New York, New York, United States of America. Department of Medical Biotechnologies, Section of Pathology, University of Siena, Siena, Italy. Department of Medical Biotechnologies, Section of Pathology, University of Siena, Siena, Italy. Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), S. Orsola-Malpighi Hospital, Bologna University School of Medicine, Bologna, Italy. Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), S. Orsola-Malpighi Hospital, Bologna University School of Medicine, Bologna, Italy. Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), S. Orsola-Malpighi Hospital, Bologna University School of Medicine, Bologna, Italy. Department of Systems Biology, Columbia University College of Physicians and Surgeons, New York, New York, United States of America. Department of Medical Biotechnologies, Section of Pathology, University of Siena, Siena, Italy. Department of Medical Biotechnologies, Section of Pathology, University of Siena, Siena, Italy; School of Biological and Chemical Sciences, Queen Mary University of London, London, United Kingdom. Department of Medical Biotechnologies, Section of Pathology, University of Siena, Siena, Italy. Department of Medical Biotechnologies, Section of Pathology, University of Siena, Siena, Italy. Department of Medical Biotechnologies, Section of Pathology, University of Siena, Siena, Italy. Department of Medical Biotechnologies, Section of Pathology, University of Siena, Siena, Italy. Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), S. Orsola-Malpighi Hospital, Bologna University School of Medicine, Bologna, Italy. Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), S. Orsola-Malpighi Hospital, Bologna University School of Medicine, Bologna, Italy. Lacor Hospital, Gulu, Uganda. Lacor Hospital, Gulu, Uganda. Moi University, Eldoret, Kenya. Moi University, Eldoret, Kenya. Moi University, Eldoret, Kenya. Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), S. Orsola-Malpighi Hospital, Bologna University School of Medicine, Bologna, Italy. Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), S. Orsola-Malpighi Hospital, Bologna University School of Medicine, Bologna, Italy; Unit of Haematopathology, European Institute of Oncology, Milan and Bologna University School of Medicine, Bologna, Italy. Department of Medical Biotechnologies, Section of Pathology, University of Siena, Siena, Italy; Department of Experimental, Diagnostic, and Specialty Medicine (DIMES), S. Orsola-Malpighi Hospital, Bologna University School of Medicine, Bologna, Italy. Department of Systems Biology, Columbia University College of Physicians and Surgeons, New York, New York, United States of America; Department of Biomedical Informatics, Columbia University College of Physicians and Surgeons, New York, New York, United States of America.", abstract = "Endemic Burkitt lymphoma (eBL) is primarily found in children in equatorial regions and represents the first historical example of a virus-associated human malignancy. Although Epstein-Barr virus (EBV) infection and MYC translocations are hallmarks of the disease, it is unclear whether other factors may contribute to its development. We performed RNA-Seq on 20 eBL cases from Uganda and showed that the mutational and viral landscape of eBL is more complex than previously reported. First, we found the presence of other herpesviridae family members in 8 cases (40\%), in particular human herpesvirus 5 and human herpesvirus 8 and confirmed their presence by immunohistochemistry in the adjacent non-neoplastic tissue. Second, we identified a distinct latency program in EBV involving lytic genes in association with TCF3 activity. Third, by comparing the eBL mutational landscape with published data on sporadic Burkitt lymphoma (sBL), we detected lower frequencies of mutations in MYC, ID3, TCF3 and TP53, and a higher frequency of mutation in ARID1A in eBL samples. Recurrent mutations in two genes not previously associated with eBL were identified in 20\% of tumors: RHOA and cyclin F (CCNF). We also observed that polyviral samples showed lower numbers of somatic mutations in common altered genes in comparison to sBL specimens, suggesting dual mechanisms of transformation, mutation versus virus driven in sBL and eBL respectively.", journal = "PLoS Pathog.", volume = 11, number = 10, pages = "e1005158", month = oct, year = 2015, keywords = "burkitt lymphoma; ebv; rna sequencing" }