Copy-number and gene dependency analysis reveals partial copy loss of wild-type SF3B1 as a novel cancer vulnerability
Author(s)
Paolella, Brenton R; Urbanski, Laura M; Alberta, John A; Bandopadhayay, Pratiti; Nichols, Caitlin A; Agarwalla, Pankaj K; Brown, Meredith S; Lamothe, Rebecca; Yu, Yong; Choi, Peter S; Obeng, Esther A; Heckl, Dirk; Vazquez, Francisca; Buhrlage, Sara J; Stiles, Charles D; Reed, Robin; Gibson, William J; Zack, Travis Ian; Wei, Guo; Wang, Belinda; Tsherniak, Aviad; Weir, Barbara A; Root, David; Cowley, Glenn S; Ebert, Benjamin L; Hahn, William; Beroukhim, Rameen; ... Show more Show less
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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.
Date issued
2017-02Department
Broad Institute of MIT and HarvardJournal
eLife
Publisher
eLife Sciences Publications, Ltd.
Citation
Paolella, Brenton R; Gibson, William J; Urbanski, Laura M; Alberta, John A; Zack, Travis I; Bandopadhayay, Pratiti; Nichols, Caitlin A et al. “Copy-Number and Gene Dependency Analysis Reveals Partial Copy Loss of Wild-Type SF3B1 as a Novel Cancer Vulnerability.” eLife 6 (February 2017): e23268 © 2017 Paolella et al
Version: Final published version
ISSN
2050-084X