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- Title
Copy-number and gene dependency analysis reveals partial copy loss of wild-type SF3B1 as a novel cancer vulnerability.
- Authors
Paolella, Brenton R.; Gibson, William J.; Urbanski, Laura M.; Alberta, John A.; Zack, Travis I.; Bandopadhayay, Pratiti; Nichols, Caitlin A.; Agarwalla, Pankaj K.; Brown, Meredith S.; Lamothe, Rebecca; Yong Yu; Choi, Peter S.; Obeng, Esther A.; Heckl, Dirk; Guo Wei; Wang, Belinda; Tsherniak, Aviad; Vazquez, Francisca; Weir, Barbara A.; Root, David E.
- 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.
- Subjects
CANCER cells; CELL lines; DNA copy number variations; SPLICEOSOMES; CELL death
- Publication
eLife, 2017, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.23268