Germ-line msh6 mutations in colorectal cancer families.
Germ-line msh6 mutations in colorectal cancer families.
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发表时间：
1999-10
期刊：
影响因子：
11.2
通讯作者：
R. Kolodner;J. Tytell;J. Schmeits;M. Kane;R. Gupta;J. Weger;S. Wahlberg;E. Fox;David Peel;A. Ziogas;J. Garber;S. Syngal;H. Anton-Culver;Frederick P. Li
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作者：
R. Kolodner;J. Tytell;J. Schmeits;M. Kane;R. Gupta;J. Weger;S. Wahlberg;E. Fox;David Peel;A. Ziogas;J. Garber;S. Syngal;H. Anton-Culver;Frederick P. Li
遗传性非息肉病性结直肠癌（HNPCC）主要是由于两个错配修复基因MSH2和MLH1的遗传突变，而其他错配修复基因的种系突变是罕见的。我们检测了140例结直肠癌患者的种系msh6突变频率，包括45例散发性病例，91例家族性非HNPCC病例和4例HNPCC病例。在91例以人群为基础的家族性非hnpcc病例中，6例患者发现种系msh6突变（分析了7.1%的先证，诊断时中位年龄为61岁）。这些突变包括一个剪接位点突变，一个移码突变，两个被证明是功能丧失突变的错义突变，以及两个无法进行功能研究的错义突变。相比之下，在以人群为基础的系列中，45例散发病例和4例HNPCC病例中，以及在58个以临床为基础的HNPCC家族的第二系列中，均未发现种系msh6突变。我们的数据表明，种系msh6突变使个体主要易患不符合HNPCC经典标准的晚发性家族性结直肠癌。
Hereditary nonpolyposis colorectal carcinoma (HNPCC) is due primarily to inherited mutations in two mismatch repair genes, MSH2 and MLH1, whereas germ-line mutations in other mismatch repair genes are rare. We examined the frequency of germ-line msh6 mutations in a population-based series of 140 colorectal cancer patients, including 45 sporadic cases, 91 familial non-HNPCC cases, and 4 HNPCC cases. Among the 91 population-based familial non-HNPCC cases, germ-line msh6 mutations were found in 6 patients (7.1% of probands analyzed; median age at diagnosis, 61 years). These mutations included a splice site mutation, a frameshift mutation, two missense mutations that were demonstrated to be loss of function mutations, and two missense mutations for which functional studies were not possible. In contrast, germ-line msh6 mutations were not found in any of the 45 sporadic cases and the 4 HNPCC cases in the population-based series or in the second series of 58 clinic-based, primarily HNPCC families. Our data suggest that germ-line msh6 mutations predispose individuals to primarily late-onset, familial colorectal carcinomas that do not fulfill classic criteria for HNPCC.