| Literature DB >> 28177281 |
Brenton R Paolella1,2,3, William J Gibson1,2,3, Laura M Urbanski1,3, John A Alberta1,4, Travis I Zack1,2,3, Pratiti Bandopadhayay1,2,3,5, Caitlin A Nichols1,2,3, Pankaj K Agarwalla6, Meredith S Brown1,3, Rebecca Lamothe1,3, Yong Yu7, Peter S Choi2,3, Esther A Obeng2,8, Dirk Heckl8, Guo Wei2, Belinda Wang2,3, Aviad Tsherniak2, Francisca Vazquez2, Barbara A Weir2, David E Root2, Glenn S Cowley2, Sara J Buhrlage1, Charles D Stiles1,4, Benjamin L Ebert2,8, William C Hahn2,3,9, Robin Reed7, Rameen Beroukhim1,2,3,9.
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.Entities:
Keywords: CYCLOPS genes; Cancer therapeutics; Copy number alterations; SF3B1; Spliceosome; Target identification and validation; cancer biology; human; human biology; medicine; mouse
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Year: 2017 PMID： 28177281 PMCID： PMC5357138 DOI： 10.7554/eLife.23268
Source DB: PubMed Journal: Elife ISSN： 2050-084X Impact factor: 8.140