The landscape of somatic copy-number alteration across human cancers.
The landscape of somatic copy-number alteration across human cancers.
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作者：
发现在肿瘤发生中起因果作用的关键基因的一种有效方法是鉴定在人类癌症中经历频繁改变的基因组区域。在这里，我们报告了来自3131例癌症标本的体细胞拷贝数改变（SCNAs）的高分辨率分析，主要属于26种组织学类型。我们确定了158个在多种癌症类型中以显著频率改变的局灶性SCNA区域，其中122个区域无法通过位于这些区域内的已知癌症靶基因的存在来解释。几个基因家族在SCNA病灶的这些区域中富集，包括凋亡调节因子BCL 2家族和NF-κB通路。我们表明，癌细胞窝藏扩增周围的MCL 1和BCL 2L 1抗凋亡基因依赖于这些基因的表达生存。最后，我们证明了在单个癌症类型中鉴定的绝大多数SCNA存在于多种癌症类型中。
A powerful way to discover key genes playing causal roles in oncogenesis is to identify genomic regions that undergo frequent alteration in human cancers. Here, we report high-resolution analyses of somatic copy-number alterations (SCNAs) from 3131 cancer specimens, belonging largely to 26 histological types. We identify 158 regions of focal SCNA that are altered at significant frequency across multiple 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-κB pathway. We show that cancer cells harboring amplifications surrounding the MCL1 and BCL2L1 anti-apoptotic genes depend upon expression of these genes for survival. Finally, we demonstrate that a large majority of SCNAs identified in individual cancer types are present in multiple cancer types.
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DOI：
10.1038/nrc1299
发表时间：
2004-03
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1073/pnas.0710052104
发表时间：
2007-12-11
影响因子：
11.1
作者：
Beroukhim, Rameen;Getz, Gad;Sellers, William R.
通讯作者：
Sellers, William R.
影响因子：
8
作者：
Lundberg, AS;Randell, SH;Hahn, WC
通讯作者：
Hahn, WC
影响因子：
--
作者：
DALCIN, P;KOOLS, P;VANDENBERGHE, H
通讯作者：
VANDENBERGHE, H
影响因子：
8
作者：
Chitale, D.;Gong, Y.;Taylor, B. S.;Broderick, S.;Brennan, C.;Somwar, R.;Golas, B.;Wang, L.;Motoi, N.;Szoke, J.;Reinersman, J. M.;Major, J.;Sander, C.;Seshan, V. E.;Zakowski, M. F.;Rusch, V.;Pao, W.;Gerald, W.;Ladanyi, M.
通讯作者：
Ladanyi, M.