Copy-number and gene dependency analysis reveals partial copy loss of wild-type SF3B1 as a novel cancer vulnerability
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Author
Urbanski, Laura M
Brown, Meredith S
Lamothe, Rebecca
Heckl, Dirk
Wei, Guo
Tsherniak, Aviad
Vazquez, Francisca
Root, David E
Cowley, Glenn S
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.7554/eLife.23268Metadata
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Paolella, B. R., W. J. Gibson, L. M. Urbanski, J. A. Alberta, T. I. Zack, P. Bandopadhayay, C. A. Nichols, et al. 2017. “Copy-number and gene dependency analysis reveals partial copy loss of wild-type SF3B1 as a novel cancer vulnerability.” eLife 6 (1): e23268. doi:10.7554/eLife.23268. http://dx.doi.org/10.7554/eLife.23268.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. DOI: http://dx.doi.org/10.7554/eLife.23268.001Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5357138/pdf/Terms of Use
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