TY - JOUR TI - Copy-number and gene dependency analysis reveals partial copy loss of wild-type SF3B1 as a novel cancer vulnerability AU - Paolella, Brenton R AU - Gibson, William J AU - Urbanski, Laura M AU - Alberta, John A AU - Zack, Travis I AU - Bandopadhayay, Pratiti AU - Nichols, Caitlin A AU - Agarwalla, Pankaj K AU - Brown, Meredith S AU - Lamothe, Rebecca AU - Yu, Yong AU - Choi, Peter S AU - Obeng, Esther A AU - Heckl, Dirk AU - Wei, Guo AU - Wang, Belinda AU - Tsherniak, Aviad AU - Vazquez, Francisca AU - Weir, Barbara A AU - Root, David E AU - Cowley, Glenn S AU - Buhrlage, Sara J AU - Stiles, Charles D AU - Ebert, Benjamin L AU - Hahn, William C AU - Reed, Robin AU - Beroukhim, Rameen A2 - Green, Michael R VL - 6 PY - 2017 DA - 2017/02/08 SP - e23268 C1 - eLife 2017;6:e23268 DO - 10.7554/eLife.23268 UR - https://doi.org/10.7554/eLife.23268 AB - 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. KW - Copy number alterations KW - Spliceosome KW - SF3B1 KW - Target identification and validation KW - CYCLOPS genes KW - Cancer therapeutics JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -