| Literature DB >> 27478040 |
Alice H Berger1,2,3, Angela N Brooks1,2,3, Xiaoyun Wu2, Yashaswi Shrestha2, Candace Chouinard2, Federica Piccioni2, Mukta Bagul2, Atanas Kamburov2,3,4, Marcin Imielinski1,2,3, Larson Hogstrom2, Cong Zhu2, Xiaoping Yang2, Sasha Pantel2, Ryo Sakai5, Jacqueline Watson1,2, Nathan Kaplan1, Joshua D Campbell1,2,3, Shantanu Singh2, David E Root2, Rajiv Narayan2, Ted Natoli2, David L Lahr2, Itay Tirosh2, Pablo Tamayo2, Gad Getz2,3,4, Bang Wong2, John Doench2, Aravind Subramanian2, Todd R Golub1,2, Matthew Meyerson1,2,3, Jesse S Boehm2.
Abstract
Recent genome sequencing efforts have identified millions of somatic mutations in cancer. However, the functional impact of most variants is poorly understood. Here we characterize 194 somatic mutations identified in primary lung adenocarcinomas. We present an expression-based variant-impact phenotyping (eVIP) method that uses gene expression changes to distinguish impactful from neutral somatic mutations. eVIP identified 69% of mutations analyzed as impactful and 31% as functionally neutral. A subset of the impactful mutations induces xenograft tumor formation in mice and/or confers resistance to cellular EGFR inhibition. Among these impactful variants are rare somatic, clinically actionable variants including EGFR S645C, ARAF S214C and S214F, ERBB2 S418T, and multiple BRAF variants, demonstrating that rare mutations can be functionally important in cancer.Entities:
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Year: 2016 PMID： 27478040 PMCID： PMC5003022 DOI： 10.1016/j.ccell.2016.06.022
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743