Copy-number and gene dependency analysis reveals partial copy loss of wild-type SF3B1 as a novel cancer vulnerability.
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| Abstract |
Genomic instability is a hallmark of human cancer, and results in widespread somatic copy number alterations. We used a genome-scale shRNA viability screen in human cancer cell lines to systematically identify genes that are essential in the context of particular copy-number alterations (copy-number associated gene dependencies). The most enriched class of copy-number associated gene dependencies was CYCLOPS (Copy-number alterations Yielding Cancer Liabilities Owing to Partial losS) genes, and spliceosome components were the most prevalent. One of these, the pre-mRNA splicing factor SF3B1, is also frequently mutated in cancer. We validated SF3B1 as a CYCLOPS gene and found that human cancer cells harboring partial SF3B1 copy-loss lack a reservoir of SF3b complex that protects cells with normal SF3B1 copy number from cell death upon partial SF3B1 suppression. These data provide a catalog of copy-number associated gene dependencies and identify partial copy-loss of wild-type SF3B1 as a novel, non-driver cancer gene dependency.
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| Authors | Brenton R Paolella, William J Gibson, Laura M Urbanski, John A Alberta, Travis I Zack, Pratiti Bandopadhayay, Caitlin A Nichols, Pankaj K Agarwalla, Meredith S Brown, Rebecca Lamothe, Yong Yu, Peter S Choi, Esther A Obeng, Dirk Heckl, Guo Wei, Belinda Wang, Aviad Tsherniak, Francisca Vazquez, Barbara A Weir, David E Root, Glenn S Cowley, Sara J Buhrlage, Charles D Stiles, Benjamin L Ebert, William C Hahn, Robin Reed, Rameen Beroukhim |
| Journal | eLife (Elife) Vol. 6 (02 08 2017) ISSN: 2050-084X [Electronic] England |
| PMID | 28177281 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't) |
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