SOMATIC MUTATIONS IN THE HMSH2 GENE IN MICROSATELLITE UNSTABLE COLORECTAL CARCINOMAS
SOMATIC MUTATIONS IN THE HMSH2 GENE IN MICROSATELLITE UNSTABLE COLORECTAL CARCINOMAS
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DOI：
10.1093/hmg/4.11.2065
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发表时间：
1995-11-01
影响因子：
3.5
通讯作者：
KOLODNER, RD
中科院分区：
文献类型：
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作者：
BORRESEN, AL;LOTHE, RA;KOLODNER, RD
微卫星不稳定性常见于遗传性非息肉性结直肠癌（HNPCC）患者的肿瘤。错配修复基因hMSH2的种系突变约占这些病例的50%。来自散发性病例的肿瘤也表现出这种微卫星不稳定表型，尽管频率较低，迄今为止在此类肿瘤中报道的体细胞衍生突变很少。在这项研究中，我们使用恒变性凝胶电泳（CDGE）对23例表现微卫星不稳定性的原发性结直肠癌（4例家族性和19例散发性）的DNA进行了hMSH2基因突变的筛选。在散发病例中，发现5例（26%）有体细胞衍生突变。一个肿瘤显示出两种不同的突变，可能导致基因的纯合失活。四个家族病例中的一个被归类为患有HNPCC，并且在该肿瘤中发现了种系和体细胞突变。这些结果表明，相当一部分具有微卫星不稳定性的散发性结直肠癌存在hMSH2基因的体细胞突变。
Microsatellite instability is frequently seen in tumors from patients with hereditary nonpolyposis colorectal cancer (HNPCC). Germline mutations in the mismatch repair gene hMSH2 account for approximately 50% of these cases. Tumors from sporadic cases also exhibit this microsatellite instability phenotype, although at a lower frequency, and very few somatically derived mutations have so far been reported in such tumors. In this study DNA from 23 primary colorectal carcinomas (four familial and 19 sporadic cases) exhibiting microsatellite instability were screened for mutations in the hMSH2 gene using constant denaturant gel electrophoresis (CDGE). Among the sporadic cases, five (26%) were found to have somatically derived mutations. One tumor revealed two different mutations, possibly leading to a homozygous inactivation of the gene. One of the four familial cases was classified as having HNPCC, and a germline as well as a somatic mutation were found in this tumor. These results demonstrate that a considerable proportion of sporadic colorectal cancers with microsatellite instability, have somatic mutations in the hMSH2 gene.