Glioblastomas (GBMs) account for nearly half of all primary malignant brain tumours, and current therapies are often only marginally effective. Our understanding of the underlying biology of these tumours and the development of new therapies have been complicated in part by widespread inter- and intratumoural heterogeneity. To explore this heterogeneity, we are performing regional subsampling of primary glioblastomas and organoids derived from these tissue samples. To identify cellular subpopulations within these tissues and organoids, we are performing single-cell RNA-sequencing (scRNA-seq) and genome sequencing on primary tumour samples and 1-3 matched organoids per sample. We have profiled samples from five tumour sets to date and have obtained sequencing data for 16,822 primary tissue cells and 11,043 organoid cells. Overall, our data will help evaluate the utility of tumour-derived organoids as model systems for GBM and will aid in identifying cellular subpopulations defined by gene expression patterns, both in primary GBM regional subsamples and their associated organoids. These analyses may also uncover novel therapeutic targets previously unrevealed through bulk analyses.

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