Defining a Cancer Dependency Map

被引：1871

作者：

Tsherniak, Aviad ^{[1
]}

Vazquez, Francisca ^{[1
,2
]}

Montgomery, Phil G. ^{[1
]}

Weir, Barbara A. ^{[1
,2
]}

Kryukov, Gregory ^{[1
,2
]}

Cowley, Glenn S. ^{[1
]}

Gill, Stanley ^{[1
,2
]}

Harrington, William F. ^{[1
]}

Pantel, Sasha ^{[1
]}

Krill-Burger, John M. ^{[1
]}

Meyers, Robin M. ^{[1
]}

Ali, Levi ^{[1
,2
,3
,4
]}

Goodale, Amy ^{[1
]}

Lee, Yenarae ^{[1
]}

Jiang, Guozhi ^{[1
]}

Hsiao, Jessica ^{[1
]}

Gerath, William F. J. ^{[1
]}

Howell, Sara ^{[1
]}

Merkel, Erin ^{[1
]}

Ghandi, Mahmoud ^{[1
]}

Garraway, Levi A. ^{[1
,5
]}

Root, David E. ^{[1
]}

Golub, Todd R. ^{[1
,2
,4
,5
]}

Boehm, Jesse S. ^{[1
]}

Hahn, William C. ^{[1
,2
,3
,4
]}

机构：

[1] Broad Inst Harvard & MIT, 415 Main St, Cambridge, MA 02142 USA

[2] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA

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

[4] Harvard Med Sch, 25 Shattuck St, Boston, MA 02115 USA

[5] Howard Hughes Med Inst, 4000 Jones Bridge Rd, Chevy Chase, MD USA

来源：

CELL | 2017年 / 170卷 / 03期

关键词：

THERAPEUTIC VULNERABILITIES; ESSENTIAL GENES; GENOME; RNAI; EXPRESSION; BREAST; IDENTIFICATION; PREDICTION; COMPLEXES; PROMOTES;

D O I：

10.1016/j.cell.2017.06.010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Most human epithelial tumors harbor numerous alterations, making it difficult to predict which genes are required for tumor survival. To systematically identify cancer dependencies, we analyzed 501 genome-scale loss-of-function screens performed in diverse human cancer cell lines. We developed DEMETER, an analytical framework that segregates on-from off-target effects of RNAi. 769 genes were differentially required in subsets of these cell lines at a threshold of six SDs from the mean. We found predictive models for 426 dependencies (55%) by nonlinear regression modeling considering 66,646 molecular features. Many dependencies fall into a limited number of classes, and unexpectedly, in 82% of models, the top biomarkers were expression based. We demonstrated the basis behind one such predictive model linking hypermethylation of the UBB ubiquitin gene to a dependency on UBC. Together, these observations provide a foundation for a cancer dependency map that facilitates the prioritization of therapeutic targets.

引用

页码：564 / +

页数：29

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