Cell
Volume 170, Issue 3, 27 July 2017, Pages 577-592.e10
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Project DRIVE: A Compendium of Cancer Dependencies and Synthetic Lethal Relationships Uncovered by Large-Scale, Deep RNAi Screening

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Highlights

  • Project DRIVE: deep RNAi interrogation of viability effects in cancer

  • ∼8,000 genes were targeted by a median of 20 shRNAs per gene in ∼400 CCLE models

  • Data robustly define cancer dependency genes falling into distinct outlier classes

  • Enables genetic networks that reveal protein complexes and biological pathways

Summary

Elucidation of the mutational landscape of human cancer has progressed rapidly and been accompanied by the development of therapeutics targeting mutant oncogenes. However, a comprehensive mapping of cancer dependencies has lagged behind and the discovery of therapeutic targets for counteracting tumor suppressor gene loss is needed. To identify vulnerabilities relevant to specific cancer subtypes, we conducted a large-scale RNAi screen in which viability effects of mRNA knockdown were assessed for 7,837 genes using an average of 20 shRNAs per gene in 398 cancer cell lines. We describe findings of this screen, outlining the classes of cancer dependency genes and their relationships to genetic, expression, and lineage features. In addition, we describe robust gene-interaction networks recapitulating both protein complexes and functional cooperation among complexes and pathways. This dataset along with a web portal is provided to the community to assist in the discovery and translation of new therapeutic approaches for cancer.

Keywords

CCLE
DRIVE
RNA interference
synthetic lethality
functional genomics
cancer dependency

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