Copy-number and gene dependency analysis reveals partial copy loss of wild-type SF3B1 as a novel cancer vulnerability
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Paolella-2017-Copy-number and gene dependency.pdf
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4.43 MB
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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
Date Issued
February 2017
Journal
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
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.
MIT Department
Broad Institute of MIT and Harvard
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Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.7554/eLife.23268
