Copy-number and gene dependency analysis reveals partial copy loss of wild-type SF3B1 as a novel cancer vulnerability.
Authors | |
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. |
Year of Publication | 2017
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Journal | Elife
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Volume | 6
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Date Published | 2017 Feb 08
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ISSN | 2050-084X
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DOI | 10.7554/eLife.23268
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PubMed ID | 28177281
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PubMed Central ID | PMC5357138
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Links | |
Grant list | R01 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
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