The role of hPMS1 and hPMS2 in predisposing to colorectal cancer.-猫眼课题宝

DOI：

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发表时间：

2001-11

期刊：

Cancer research

影响因子：

11.2

通讯作者：

中科院分区：

医学1区

文献类型：

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作者：

Tao Liu;Hai Yan;S. Kuismanen;Antonio Percesepe;M. Bisgaard;M. Pedroni;P. Benatti;K. Kinzler;B. Vogelstein;M. P. D. Leon;P. Peltomäki;Annika Lindblom

遗传性非息肉病性结直肠癌（HNPCC）可归因于错配修复缺陷。DNA错配修复失活是结直肠癌微卫星不稳定性的基础。三种DNA错配修复基因hMSH2、hMLH1和hMSH6的种系突变被发现在HNPCC和HNPCC样家族中分离。两个DNA错配修复基因hPMS1和hPMS2也被认为易患HNPCC。在这项研究中，84例HNPCC和HNPCC样系在其他三个已知DNA错配修复基因中没有已知突变，筛选了hPMS1或hPMS2基因的种系突变。未发现明确的致病突变。转化技术被用来检测hMSH2的两个受影响的家族成员的大缺失，其中hPMS1突变最初被报道，而hPMS1突变只存在于这两个个体中的一个。自从hPMS1和hPMS2基因首次被报道以来，hPMS2的种系突变主要在Turcot综合征患者中得到证实。然而，没有发现这两个基因中的任何一个突变在HNPCC家族中分离。在有更好的证据表明这些基因的种系突变与结直肠癌风险增加有关之前，建议对这些基因突变的作用采取保守的解释。

Hereditary nonpolyposis colorectal cancer (HNPCC) is attributable to a deficiency of mismatch repair. Inactivation of DNA mismatch repair underlies the genesis of microsatellite instability in colorectal cancer. Germline mutations in three DNA mismatch repair genes, hMSH2, hMLH1, and hMSH6, have been found to segregate in HNPCC and HNPCC-like families. The two DNA mismatch repair genes hPMS1 and hPMS2 have also been suggested to predispose to HNPCC. In this study, 84 HNPCC and HNPCC-like kindreds without known mutations in the other three known DNA mismatch repair genes were screened for germline mutations in the hPMS1 or hPMS2 gene. No clear-cut pathogenic mutations were identified. Conversion technology was used to detect a large hMSH2 deletion in two affected members of the kindred in which the hPMS1 mutation was originally reported, whereas the hPMS1 mutation was only present in one of these two individuals. Since the hPMS1 and hPMS2 genes were first reported, germline mutations in hPMS2 have been demonstrated primarily in patients with Turcot's syndrome. However, no mutation in any of the two genes has been found to segregate in HNPCC families. Until there is better evidence for an increased colorectal cancer risk associated with germline mutations in these genes, a conservative interpretation of the role of mutations in these genes is advised.