Novartis Institutes for Biomedical Research, Oncology Disease Area, Basel 4002, Switzerland; Cambridge, MA 02139, USA; and Emeryville, CA 94608, USA.
Novartis Institutes for Biomedical Research, Oncology Disease Area, Basel 4002, Switzerland; Cambridge, MA 02139, USA; and Emeryville, CA 94608, USA.
Cell. 2017 Jul 27;170(3):577-592.e10. doi: 10.1016/j.cell.2017.07.005.
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.
人类癌症的突变全景图的阐明进展迅速，并伴随着针对突变致癌基因的治疗方法的发展。然而，癌症依赖性的全面图谱却滞后了，需要发现对抗肿瘤抑制基因丢失的治疗靶点。为了确定与特定癌症亚型相关的弱点，我们进行了大规模的 RNAi 筛选，使用平均每个基因 20 个 shRNA，在 398 个癌细胞系中评估了 7837 个基因的 mRNA 敲低的存活效应。我们描述了这个筛选的发现，概述了癌症依赖性基因的类别及其与遗传、表达和谱系特征的关系。此外，我们还描述了稳健的基因相互作用网络，再现了蛋白质复合物以及复合物和途径之间的功能协作。这个数据集以及一个网络门户提供给社区，以协助发现和转化癌症的新治疗方法。
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