Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center.
Nature. 2010 Feb 18;463(7283):899-905. doi: 10.1038/nature08822.
A powerful way to discover key genes with causal roles in oncogenesis is to identify genomic regions that undergo frequent alteration in human cancers. Here we present high-resolution analyses of somatic copy-number alterations (SCNAs) from 3,131 cancer specimens, belonging largely to 26 histological types. We identify 158 regions of focal SCNA that are altered at significant frequency across several cancer types, of which 122 cannot be explained by the presence of a known cancer target gene located within these regions. Several gene families are enriched among these regions of focal SCNA, including the BCL2 family of apoptosis regulators and the NF-kappaBeta pathway. We show that cancer cells containing amplifications surrounding the MCL1 and BCL2L1 anti-apoptotic genes depend on the expression of these genes for survival. Finally, we demonstrate that a large majority of SCNAs identified in individual cancer types are present in several cancer types.
发现与肿瘤发生有因果关系的关键基因的一种有力方法是鉴定在人类癌症中经常发生改变的基因组区域。在这里，我们呈现了来自 3131 个癌症标本的体细胞拷贝数改变（SCNAs）的高分辨率分析，这些标本主要属于 26 种组织学类型。我们鉴定了 158 个局灶性 SCNAs 区域，这些区域在几种癌症类型中发生改变的频率很高，其中 122 个不能用位于这些区域内的已知癌症靶基因的存在来解释。在这些局灶性 SCNAs 区域中富集了几个基因家族，包括凋亡调节剂 BCL2 家族和 NF-kappaBeta 途径。我们表明，含有围绕抗凋亡基因 MCL1 和 BCL2L1 的扩增的癌细胞依赖于这些基因的表达来存活。最后，我们证明在个体癌症类型中鉴定的大多数 SCNAs 存在于几种癌症类型中。
