Abstract 197: Identifying a novel network of driver genes in glioblastoma

The purpose of this study is to identify novel genes that drive proliferation in glioblastoma (GBM) and likely contribute to gliomagenesis, therefore facilitating the aggressive nature of the tumor. GBM is an aggressive primary malignancy of the brain with almost a 100% recurrence rate. It is the most common malignant brain tumor in adults, with an average survival of 21 months after diagnosis, with the current standard of care. As such, new advances in therapy are desperately needed. Large scale genomic approaches have shown that GBM has a complex genetic architecture, with a great deal of intratumoral heterogeneity. However, a more comprehensive understanding of determinants of growth is required to identify new targets and provide new therapeutic strategies. CRISPR-Cas9 screening technology has enabled whole-genome screens that allow for systematic and objective identification of genes governing cell viability and proliferation. These genes may represent unique vulnerabilities that can be targeted with novel therapeutics. Here, we performed a genome-wide CRISPR knockout screen in SNB19 human GBM cells, covering 17,000 genes with 4 guides per gene. In this type of screen, we anticipate that those guides that are depleted over time are the ones that correspond to genes driving growth and proliferation of GBM cells. Initial analysis showed that there was a reduction in guides for known driver genes, as we might expect. However, in addition to known drivers, we were able to identify a list of approximately 150 new genes that showed significant depletion in our screen (p