Essential Gene Profiles in Breast, Pancreatic, and Ovarian Cancer Cells

被引：237

作者：

Marcotte, Richard ^{[5
]}

Brown, Kevin R. ^{[1
,2
]}

Suarez, Fernando ^{[5
]}

Sayad, Azin ^{[1
,2
]}

Karamboulas, Konstantina ^{[1
,2
]}

Krzyzanowski, Paul M. ^{[5
]}

Sircoulomb, Fabrice ^{[5
]}

Medrano, Mauricio ^{[4
,5
]}

Fedyshyn, Yaroslav ^{[1
,2
]}

Koh, Judice L. Y. ^{[1
,2
]}

van Dyk, Dewald ^{[1
,2
]}

Fedyshyn, Bohdana ^{[1
,2
]}

Luhova, Marianna ^{[1
,2
]}

Brito, Glauber C. ^{[1
,2
]}

Vizeacoumar, Franco J. ^{[1
,2
]}

Vizeacoumar, Frederick S. ^{[6
]}

Datti, Alessandro ^{[6
,8
]}

Kasimer, Dahlia ^{[1
,2
]}

Buzina, Alla ^{[1
,2
]}

Mero, Patricia ^{[1
,2
]}

Misquitta, Christine ^{[1
,2
]}

Normand, Josee ^{[5
]}

Haider, Maliha ^{[5
]}

Ketela, Troy ^{[1
,2
]}

Wrana, Jeffrey L. ^{[3
,6
]}

Rottapel, Robert ^{[4
,5
,7
]}

Neel, Benjamin G. ^{[4
,5
]}

Moffat, Jason ^{[1
,2
,3
]}

机构：

[1] Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada

[2] Univ Toronto, Banting & Best Dept Med Res, Toronto, ON M5S 3E1, Canada

[3] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 3E1, Canada

[4] Univ Toronto, Dept Med Biophys, Toronto, ON M5S 3E1, Canada

[5] Univ Hlth Network, Princess Margaret Hosp, Ontario Canc Inst, Campbell Family Canc Res Inst, Toronto, ON, Canada

[6] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada

[7] St Michaels Hosp, Dept Med, Div Rheumatol, Toronto, ON M5B 1W8, Canada

[8] Univ Perugia, Dept Expt Med & Biochem Sci, I-06100 Perugia, Italy

来源：

CANCER DISCOVERY | 2012年 / 2卷 / 02期

关键词：

GENOME-WIDE RNAI; TYROSINE KINASE; H-PRUNE; EXPRESSION; AMPLIFICATION; COMPLEX; MUTATIONS; PROTEIN; TARGET; EIF3S3;

D O I：

10.1158/2159-8290.CD-11-0224

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Genomic analyses are yielding a host of new information on the multiple genetic abnormalities associated with specific types of cancer. A comprehensive description of cancer-associated genetic abnormalities can improve our ability to classify tumors into clinically relevant subgroups and, on occasion, identify mutant genes that drive the cancer phenotype ("drivers"). More often, though, the functional significance of cancer-associated mutations is difficult to discern. Genome-wide pooled short hairpin RNA (shRNA) screens enable global identification of the genes essential for cancer cell survival and proliferation, providing a "functional genomic" map of human cancer to complement genomic studies. Using a lentiviral shRNA library targeting -16,000 genes and a newly developed, dynamic scoring approach, we identified essential gene profiles in 72 breast, pancreatic, and ovarian cancer cell lines. Integrating our results with current and future genomic data should facilitate the systematic identification of drivers, unanticipated synthetic lethal relationships, and functional vulnerabilities of these tumor types.

引用

页码：172 / 189

页数：18

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