Mismatch repair and the hereditary non-polyposis colorectal cancer syndrome (HNPCC)
Mismatch repair and the hereditary non-polyposis colorectal cancer syndrome (HNPCC)
复制标题
DOI：
10.1081/cnv-120000371
复制
发表时间：
2002-01-01
影响因子：
2.4
通讯作者：
Fishel, R
中科院分区：
文献类型：
--
作者：
M端ller, A;Fishel, R
遗传性非息肉病性结直肠癌 (HNPCC) 综合征是遗传性结直肠癌最常见的形式，占结直肠癌总负担的 2-7%。由于 HNPCC 没有特定的单一临床特征，因此诊断基于石油家族史（阿姆斯特丹或贝塞斯达标准），并通过检测其中一个负责错配修复 (MMR) 基因的突变来确认。可以区分两种类型的 HNPCC 家族。 1 型 HNPCC 肿瘤仅位于结肠，而在 II 型 HNPCC 患者中，结肠外肿瘤存在于胃、子宫内膜、卵巢和泌尿道。酵母错配修复基因 hMSH2、hMSH3、hMSH6、lMLH1、hMLH3、hPMS1 (scMLH2) 和 hPMS2 (scPMS1) 的人类同源物的鉴定为基因筛查提供了前景，从而导致对 HNPCC 家族突变的广泛搜索。大多数改变存在于 hMSH2 (40%) 和 hMLH1 (40%) 基因中。其他 MMR 基因的突变似乎罕见、不存在和/或与非典型家族相关 (1-5%)。由于错配修复缺陷，复制错误掺入错误不断累积，导致突变表型。 HNPCC 相关复制错误的诊断最容易，通过检查美国国家癌症研究所 (NCI) 推荐的 41 个组的简单重复序列（微卫星）并结合免疫组织化学分析来确定。尽管这些患者肿瘤发展的确切分子机制仍知之甚少，但识别具有微卫星不稳定性的肿瘤具有临床和预后意义。
The hereditary non-polyposis colorectal cancer (HNPCC)-syndrome is the Most common form of hereditary colorectal cancers, and accounts for 2-7% of the total colorectal cancer burden. Since there are no single clinical features specific for HNPCC, diagnosis is based oil family history (Amsterdam or Bethesda criteria) and is confirmed by the detection of a mutation in one of the responsible mismatch repair (MMR) genes. Two types of HNPCC-families can be distinguished. Type 1 HNPCC tumors are exclusively located in the colon, whereas in Type II HNPCC patients, extracolonic tumors are present ill the stomach, endometrium, ovary, and urinary tract. The identification of the human homologues of yeast mismatch repair genes hMSH2, hMSH3, hMSH6, lMLH1, hMLH3, hPMS1 (scMLH2), and hPMS2 (scPMS1) offered the prospect of genetic screening leading to all extensive search for mutations ill HNPCC-families. The majority of the alterations have been found in hMSH2 (40%) and hMLH1 (40%) genes. Mutations in the other MMR genes appear rare, absent, and/or associated with atypical families (1-5%). As a result of the mismatch repair deficiency replication misincorporation errors accumulate, resulting in a mutator phenotype. Diagnosis of HNPCC-associated replication errors is most easily, determined by the examination of 41 panel of the National Cancer Institute (NCI)-recommended simple repeated sequences (microsatellites), combined with immunohistochemical analysis. Although the exact molecular mechanism of the tumor development in these patients remains poorly understood, the identification of tumors that harbor a microsatellite instability has clinical and prognostic implications.