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Elife DOI:10.7554/eLife.23268

Copy-number and gene dependency analysis reveals partial copy loss of wild-type SF3B1 as a novel cancer vulnerability.

Publication TypeJournal Article
Year of Publication2017
AuthorsPaolella, BR, Gibson, WJ, Urbanski, LM, Alberta, JA, Zack, TI, Bandopadhayay, P, Nichols, CA, Agarwalla, PK, Brown, MS, Lamothe, R, Yu, Y, Choi, PS, Obeng, EA, Heckl, D, Wei, G, Wang, B, Tsherniak, A, Vazquez, F, Weir, BA, Root, DE, Cowley, GS, Buhrlage, SJ, Stiles, CD, Ebert, BL, Hahn, WC, Reed, R, Beroukhim, R
Date Published2017 Feb 08

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.


Alternate JournalElife
PubMed ID28177281
PubMed Central IDPMC5357138
Grant ListR01 CA188228 / CA / NCI NIH HHS / United States
U01 CA176058 / CA / NCI NIH HHS / United States
F30 CA192725 / CA / NCI NIH HHS / United States
R01 GM043375 / GM / NIGMS NIH HHS / United States
F32 CA180653 / CA / NCI NIH HHS / United States