Next-generation characterization of the Cancer Cell Line Encyclopedia
Next-generation characterization of the Cancer Cell Line Encyclopedia
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DOI：
10.1038/s41586-019-1186-3
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发表时间：
2019-05-23
期刊：
影响因子：
64.8
通讯作者：
Sellers, William R.
中科院分区：
文献类型：
--
作者：
Ghandi, Mahmoud;Huang, Franklin W.;Sellers, William R.
包括癌细胞系百科全书（CCLE）在内的大量全面表征的人类癌症模型提供了一个严格的框架，用于研究遗传变异、候选靶点、小分子和生物疗法，并确定新的标志物驱动的癌症依赖性。为了提高我们对导致癌症表型的分子特征的理解，包括药物反应，我们扩大了癌细胞系的特征，包括遗传、RNA剪接、DNA甲基化、组蛋白H3修饰、microRNA表达和来自不同谱系和种族的1,072个细胞系的反相蛋白阵列数据。将这些数据与药物敏感性、短发夹RNA敲除和CRISPR-Cas9敲除等功能特征相结合，揭示了癌症药物和相关生物标志物的潜在靶点。总之，该数据集和附带的公共数据门户为使用模型癌细胞系加速癌症研究提供了资源。
Large panels of comprehensively characterized human cancer models, including the Cancer Cell Line Encyclopedia (CCLE), have provided a rigorous framework with which to study genetic variants, candidate targets, and small-molecule and biological therapeutics and to identify new marker-driven cancer dependencies. To improve our understanding of the molecular features that contribute to cancer phenotypes, including drug responses, here we have expanded the characterizations of cancer cell lines to include genetic, RNA splicing, DNA methylation, histone H3 modification, microRNA expression and reverse-phase protein array data for 1,072 cell lines from individuals of various lineages and ethnicities. Integration of these data with functional characterizations such as drug-sensitivity, short hairpin RNA knockdown and CRISPR-Cas9 knockout data reveals potential targets for cancer drugs and associated biomarkers. Together, this dataset and an accompanying public data portal provide a resource for the acceleration of cancer research using model cancer cell lines.