Broad Institute of Harvard and MIT, Cambridge, Massachusetts. Department of Medical Oncology and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts.
Department of Cardiothoracic Surgery, NYU Langone Medical Center, New York, New York.
Cancer Res. 2015 Jan 15;75(2):264-9. doi: 10.1158/0008-5472.CAN-14-1008. Epub 2014 Dec 8.
Malignant pleural mesothelioma (MPM) is an aggressive neoplasm associated with asbestos exposure. Although previous studies based on candidate gene approaches have identified important common somatic mutations in MPM, these studies have focused on small sets of genes and have provided a limited view of the genetic alterations underlying this disease. Here, we performed whole-exome sequencing on DNA from 22 MPMs and matched blood samples, and identified 517 somatic mutations across 490 mutated genes. Integrative analysis of mutations and somatic copy-number alterations revealed frequent genetic alterations in BAP1, NF2, CDKN2A, and CUL1. Our study presents the first unbiased view of the genomic basis of MPM.
恶性胸膜间皮瘤（MPM）是一种与石棉暴露相关的侵袭性肿瘤。虽然以前基于候选基因方法的研究已经确定了 MPM 中的重要常见体细胞突变，但这些研究集中在少数基因上，对导致这种疾病的遗传改变提供了有限的认识。在这里，我们对 22 例 MPM 及其匹配的血液样本的 DNA 进行了全外显子组测序，鉴定了 490 个突变基因中的 517 个体细胞突变。对突变和体细胞拷贝数改变的综合分析揭示了 BAP1、NF2、CDKN2A 和 CUL1 中频繁的遗传改变。我们的研究展示了 MPM 基因组基础的第一个无偏视图。
