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

被引：59

作者：

Paolella, Brenton R. ^{[1
,2
,3
,4
,5
]}

Gibson, William J. ^{[1
,2
,3
,4
,5
]}

Urbanski, Laura M. ^{[1
,2
,5
]}

Alberta, John A. ^{[1
,2
,6
]}

Zack, Travis I. ^{[1
,2
,3
,4
,5
]}

Bandopadhayay, Pratiti ^{[1
,2
,3
,4
,5
,7
]}

Nichols, Caitlin A. ^{[1
,2
,3
,4
,5
]}

Agarwalla, Pankaj K. ^{[8
]}

Brown, Meredith S. ^{[1
,2
,5
]}

Lamothe, Rebecca ^{[1
,2
,5
]}

Yu, Yong ^{[9
]}

Choi, Peter S. ^{[2
,3
,4
,5
]}

Obeng, Esther A. ^{[3
,4
,10
]}

Heckl, Dirk ^{[10
]}

Wei, Guo ^{[3
,4
]}

Wang, Belinda ^{[2
,3
,4
,5
]}

Tsherniak, Aviad ^{[3
,4
]}

Vazquez, Francisca ^{[3
,4
]}

Weir, Barbara A. ^{[3
,4
]}

Root, David E. ^{[3
,4
]}

Cowley, Glenn S. ^{[3
,4
]}

Buhrlage, Sara J. ^{[1
,2
]}

Stiles, Charles D. ^{[1
,2
,6
]}

Ebert, Benjamin L. ^{[3
,4
,10
]}

Hahn, William C. ^{[2
,3
,4
,5
,11
]}

Reed, Robin ^{[9
]}

Beroukhim, Rameen ^{[1
,2
,3
,4
,5
,11
]}

机构：

[1] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA

[2] Harvard Med Sch, Boston, MA 02115 USA

[3] MIT, Broad Inst Massachusetts, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[4] Harvard Univ, Cambridge, MA 02138 USA

[5] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[6] Harvard Med Sch, Dept Neurobiol, Boston, MA USA

[7] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

[8] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA USA

[9] Harvard Med Sch, Dept Cell Biol, Boston, MA 02115 USA

[10] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA USA

[11] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA

来源：

ELIFE | 2017年 / 6卷

关键词：

PRE-MESSENGER-RNA; IN-VIVO; BRANCH POINT; U2; SNRNP; RING SIDEROBLASTS; IMAGE-ANALYSIS; SPLICEOSOME; PROTEIN; MYELODYSPLASIA; MUTATIONS;

D O I：

10.7554/eLife.23268

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：35

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