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Cancer Discov. 2012 Feb;2(2):172-189. doi: 10.1158/2159-8290.CD-11-0224. Epub 2011 Dec 29.

Essential gene profiles in breast, pancreatic, and ovarian cancer cells.

Author information

1
Campbell Family Cancer Research Institute, Ontario Cancer Institute, Princess Margaret Hospital University Health Network, Toronto, Canada.
2
Donnelly Centre and Banting & Best Department of Medical Research, University of Toronto, Toronto, Canada.
3
Ontario Institute for Cancer Research, Toronto, Canada.
4
Department of Medical Biophysics, University of Toronto, Toronto, Canada.
5
Samuel Lunenfeld Research Institute, Toronto, Canada.
6
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
7
Department of Molecular Genetics, University of Toronto, Toronto, Canada.
#
Contributed equally

Abstract

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.

SIGNIFICANCE:

This study presents a resource of genome-scale, pooled shRNA screens for 72 breast, pancreatic, and ovarian cancer cell lines that will serve as a functional complement to genomics data, facilitate construction of essential gene profiles, help uncover synthetic lethal relationships, and identify uncharacterized genetic vulnerabilities in these tumor types.

SIGNIFICANCE:

This study presents a resource of genome-scale, pooled shRNA screens for 72 breast, pancreatic, and ovarian cancer cell lines that will serve as a functional complement to genomics data, facilitate construction of essential gene profiles, help uncover synthetic lethal relationships, and identify uncharacterized genetic vulnerabilities in these tumor types.

PMID:
22585861
PMCID:
PMC5057396
DOI:
10.1158/2159-8290.CD-11-0224
[Indexed for MEDLINE]
Free PMC Article

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