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

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...

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Detalles Bibliográficos
Autores principales: Paolella, Brenton R, Gibson, William J, Urbanski, Laura M, Alberta, John A, Zack, Travis I, Bandopadhayay, Pratiti, Nichols, Caitlin A, Agarwalla, Pankaj K, Brown, Meredith S, Lamothe, Rebecca, Yu, Yong, Choi, Peter S, Obeng, Esther A, Heckl, Dirk, Wei, Guo, Wang, Belinda, Tsherniak, Aviad, Vazquez, Francisca, Weir, Barbara A, Root, David E, Cowley, Glenn S, Buhrlage, Sara J, Stiles, Charles D, Ebert, Benjamin L, Hahn, William C, Reed, Robin, Beroukhim, Rameen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5357138/
https://www.ncbi.nlm.nih.gov/pubmed/28177281
http://dx.doi.org/10.7554/eLife.23268
Descripción
Sumario: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.23268.001