Prevalence of somatic alterations in the colorectal cancer cell genome
Prevalence of somatic alterations in the colorectal cancer cell genome
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DOI：
10.1073/pnas.261714699
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发表时间：
2002-03-05
影响因子：
11.1
通讯作者：
Velculescu, VE
中科院分区：
文献类型：
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作者：
Wang, TL;Rago, C;Velculescu, VE
尽管一小部分人类癌症由于已知的DNA修复缺陷而增加了体细胞突变率，但对绝大多数人类癌症中体细胞改变的流行程度知之甚少。为了系统地评估结直肠肿瘤的非同义体细胞改变，我们使用DNA测序分析了大约3.2 Mb的编码肿瘤DNA，包括来自470个基因的1,811个外显子。总的来说，我们只发现了三个不同的体细胞突变，包括两个错义变化和一个14bp缺失，每个突变都在不同的基因中。每Mb肿瘤DNA中大约一个非同义体细胞变化的积累与肿瘤细胞中与正常细胞相似的突变率是一致的。这些数据表明，大多数散发性结直肠癌在核苷酸水平上不表现出突变表型。它们对于解释候选肿瘤抑制基因的体细胞突变也有重要意义。
Although a small fraction of human cancers have increased rates of somatic mutation because of known deficiencies in DNA repair, little is known about the prevalence of somatic alterations in the vast majority of human cancers. To systematically assess nonsynonymous somatic alterations in colorectal neoplasia, we used DNA sequencing to analyze approximate to3.2 Mb of coding tumor DNA comprising 1,811 exons from 470 genes. In total, we identified only three distinct somatic mutations, comprising two missense changes and one 14-bp deletion, each in a different gene. The accumulation of approximately one nonsynonymous somatic change per Mb of tumor DNA is consistent with a rate of mutation in tumor cells that is similar to that of normal cells. These data suggest that most sporadic colorectal cancers do not display a mutator phenotype at the nucleotide level. They also have significant implications for the interpretation of somatic mutations in candidate tumor-sup pressor genes.