MUTATION OF A MUTL HOMOLOG IN HEREDITARY COLON-CANCER
MUTATION OF A MUTL HOMOLOG IN HEREDITARY COLON-CANCER
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DOI：
10.1126/science.8128251
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发表时间：
1994-03-18
期刊：
影响因子：
56.9
通讯作者：
VOGELSTEIN, B
中科院分区：
文献类型：
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作者：
PAPADOPOULOS, N;NICOLAIDES, NC;VOGELSTEIN, B
遗传性非息肉病性结直肠癌(HNPCC)的一些病例是由于与MutS相关的错配修复基因的改变。对来自随机互补DNA克隆的表达序列标签的大型数据库进行搜索后，发现了另外三个人类错配修复基因，它们都与细菌的muL基因有关。其中一个基因(HMLH1)位于染色体3p21上，位于先前与HNPCC家族癌症易感性有关的标记的1厘米范围内。在这些家系中发现了会破坏基因产物的hMLH1突变，证明了该基因与疾病有关。这些结果表明，几个错配修复基因中的任何一个的缺陷都可以引起HNPCC。
Some cases of hereditary nonpolyposis colorectal cancer (HNPCC) are due to alterations in a mutS-related mismatch repair gene. A search of a large database of expressed sequence tags derived from random complementary DNA clones revealed three additional human mismatch repair genes, all related to the bacterial mutL gene. One of these genes (hMLH1) resides on chromosome 3p21, within 1 centimorgan of markers previously linked to cancer susceptibility in HNPCC kindreds. Mutations of hMLH1 that would disrupt the gene product were identified in such kindreds, demonstrating that this gene is responsible for the disease. These results suggest that defects in any of several mismatch repair genes can cause HNPCC.