MUTATIONS OF 2 PMS HOMOLOGS IN HEREDITARY NONPOLYPOSIS COLON-CANCER
MUTATIONS OF 2 PMS HOMOLOGS IN HEREDITARY NONPOLYPOSIS COLON-CANCER
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DOI：
10.1038/371075a0
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发表时间：
1994-09-01
期刊：
影响因子：
64.8
通讯作者：
KINZLER, KW
中科院分区：
文献类型：
--
作者：
NICOLAIDES, NC;PAPADOPOULOS, N;KINZLER, KW
遗传性非息肉病性结直肠癌（HNPCC）是人类最常见的遗传性疾病之一（1）。几项研究表明，在这种疾病的发病机制中存在DNA错配修复缺陷（2-8）。特别地，细菌DNA错配修复基因mutS和mutL的hMSH 2和hMLH 1同源物分别显示在HNPCC病例的子集中突变（9-16）。在这里，我们报告的核苷酸序列，染色体定位和突变分析的hPMS 1和hPMS 2，两个额外的同源原核mutL基因。在HNPCC患者的生殖系中发现hPMS 1和hPMS 2均发生突变。这使HNPCC中涉及的基因数量增加了一倍，并可能有助于解释这种疾病相对较高的发病率。
HEREDITARY nonpolyposis colorectal cancer (HNPCC) is one of man's commonest hereditary diseases(1). Several studies have implicated a defect in DNA mismatch repair in the pathogenesis of this disease(2-8). In particular, hMSH2 and hMLH1 homologues of the bacterial DNA mismatch repair genes mutS and mutL, respectively, were shown to be mutated in a subset of HNPCC cases(9-16). Here we report the nucleotide sequence, chromosome localization and mutational analysis of hPMS1 and hPMS2, two additional homologues of the prokaryotic mutL gene. Both hPMS1 and hPMS2 were found to be mutated in the germline of HNPCC patients. This doubles the number of genes implicated in HNPCC and may help explain the relatively high incidence of this disease.