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Project DRIVE: A Compendium of Cancer Dependencies and Synthetic Lethal Relationships Uncovered by Large-Scale, Deep RNAi Screening

2017; Cell Press; Volume: 170; Issue: 3 Linguagem: Inglês

10.1016/j.cell.2017.07.005

1097-4172

E. Robert McDonald, Antoine de Weck, Michael R. Schlabach, Éric Billy, Konstantinos J. Mavrakis, Gregory R. Hoffman, Dhiren Belur, Deborah Castelletti, Elizabeth Frias, Kalyani Gampa, Javad Golji, Iris Kao, Li Li, Philippe Megel, Thomas A. Perkins, Nadire Ramadan, David A. Ruddy, Serena J. Silver, Sosathya Sovath, Mark Stump, Odile Weber, Roland Widmer, Jianjun Yu, Kristine Yu, Yingzi Yue, Dorothée Abramowski, Elizabeth Ackley, Rosemary Barrett, Joel P. Berger, Julie L. Bernard, Rebecca Billig, Saskia M. Brachmann, Frank P. Buxton, Roger Caothien, Justina X. Caushi, Franklin Chung, Marta Cortés-Cros, Rosalie deBeaumont, Clara Delaunay, Aurore Desplat, William Duong, Donald A. Dwoske, Richard S. Eldridge, Ali Farsidjani, Fei Feng, Jiajia Feng, Daisy Flemming, William C. Forrester, Giorgio Giacomo Galli, Zhenhai Gao, François Gauter, Veronica Gibaja, Kristy Haas, Marc Hattenberger, Tami Hood, Kristen E. Hurov, Zainab Jagani, Mathias Jenal, Jennifer Johnson, Michael D. Jones, Avnish Kapoor, Joshua M. Korn, Jilin Liu, Qiumei Liu, Shumei Liu, Yue Liu, Alice Loo, Kaitlin J. Macchi, Typhaine Martin, Gregory McAllister, Amandine Meyer, Sandra Mollé, Raymond Pagliarini, Tanushree Phadke, Brian Repko, Tanja Schouwey, Fergus Shanahan, Qiong Shen, Christelle Stamm, Christine Stephan, Volker M. Stucke, Ralph Tiedt, Malini Varadarajan, K. Venkatesan, Alberto C. Vitari, Marco Wallroth, Jan Weiler, Jing Zhang, Craig Mickanin, Vic E. Myer, Jeffery A. Porter, Albert Lai, Hans Bitter, Emma Lees, Nicholas Keen, Audrey Kauffmann, Frank Stegmeier, Francesco Hofmann, Tobias Schmelzle, William R. Sellers,

Bioinformatics and Genomic Networks

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.