Characterizing the cancer genome in lung adenocarcinoma
Characterizing the cancer genome in lung adenocarcinoma
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DOI：
10.1038/nature06358
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发表时间：
2007-12-06
期刊：
影响因子：
64.8
通讯作者：
Meyerson, Matthew
中科院分区：
文献类型：
--
作者：
Weir, Barbara A.;Woo, Michele S.;Meyerson, Matthew
细胞DNA的体细胞变化是几乎所有人类癌症的基础(1)。靶向治疗的前景(2)和高分辨率、全基因组方法的发展(3-8)现在正在刺激系统的努力来表征癌症基因组。在这里，我们报告了一个大规模的项目，以表征原发肺腺癌的拷贝数变化。通过使用密集单核苷酸多态阵列对大量肿瘤(n=371)进行分析，我们识别出总共57个显著的复发事件。我们发现，在39条常染色体臂中，有26条显示出一致的大规模拷贝数增减，其中只有少数与特定基因有关。我们还确定了31个复发的焦点事件，包括24个扩增和7个纯合子缺失。目前，这些焦点事件中只有6个与肺癌的已知突变有关。最常见的事件，染色体14q13.3的扩增，在大约12%的样本中被发现。在基因组和功能分析的基础上，我们确定NKX2-1(NK2 Homeobox 1，也称为TITF1)是一个新的候选原癌基因，它位于最小的14q13.3扩增区间，编码一种谱系特异的转录因子，与肺腺癌的很大一部分有关。更广泛地说，我们的结果表明，许多与肺腺癌有关的基因仍有待发现。
Somatic alterations in cellular DNA underlie almost all human cancers(1). The prospect of targeted therapies(2) and the development of high-resolution, genome-wide approaches(3-8) are now spurring systematic efforts to characterize cancer genomes. Here we report a large-scale project to characterize copy-number alterations in primary lung adenocarcinomas. By analysis of a large collection of tumours ( n = 371) using dense single nucleotide polymorphism arrays, we identify a total of 57 significantly recurrent events. We find that 26 of 39 autosomal chromosome arms show consistent large-scale copy-number gain or loss, of which only a handful have been linked to a specific gene. We also identify 31 recurrent focal events, including 24 amplifications and 7 homozygous deletions. Only six of these focal events are currently associated with known mutations in lung carcinomas. The most common event, amplification of chromosome 14q13.3, is found in similar to 12% of samples. On the basis of genomic and functional analyses, we identify NKX2-1 ( NK2 homeobox 1, also called TITF1), which lies in the minimal 14q13.3 amplification interval and encodes a lineage-specific transcription factor, as a novel candidate proto-oncogene involved in a significant fraction of lung adenocarcinomas. More generally, our results indicate that many of the genes that are involved in lung adenocarcinoma remain to be discovered.