Mutations predisposing to hereditary nonpolyposis colorectal cancer: Database and results of a collaborative study
Mutations predisposing to hereditary nonpolyposis colorectal cancer: Database and results of a collaborative study
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DOI：
10.1053/gast.1997.v113.pm9322509
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发表时间：
1997-10-01
期刊：
影响因子：
29.4
通讯作者：
Wijnen, J
中科院分区：
文献类型：
--
作者：
Peltomaki, P;Vasen, HFA;Wijnen, J
背景与目的：已知四种DNA错配修复基因的种系突变可导致遗传性非息肉病性结直肠癌（HNPCC）的易感性。关于这些突变的快速增长的信息需要被收集和适当地储存，以促进对这些发现的生物学和临床意义的进一步研究。方法：HNPCC国际合作小组建立了DNA错配修复基因突变和多态性数据库。在本报告中，分析了126个易感突变。结果：大部分突变发生在Mut L同源物（MLH） 1 （n = 75）或Mut S同源物（MSH） 2 (n = 48)，分布相当均匀，在MSH2外显子12和MLH1外显子16上有聚集。大多数MSH2突变包括移码（60%）或无义改变（23%），而MLH1主要受移码（40%）或错义改变（31%）的影响。虽然大多数突变是独特的，但也发现了一些常见的重复突变。在所研究的家庭（n = 202）中，82%符合阿姆斯特丹标准，15%不符合；两组的总体突变谱相似。结论：突变谱的构建将促进HNPCC诊断策略的发展。
Background & Aims: Germline mutations in four DNA mismatch repair genes are known to cause susceptibility to hereditary nonpolyposis colorectal cancer (HNPCC). The rapidly increasing information about these mutations needs to be collected and appropriately stored to facilitate further studies on the biological and clinical significance of the findings. Methods: The International Collaborative Group on HNPCC has established a database of DNA mismatch repair gene mutations and polymorphisms. In this report, 126 predisposing mutations were analyzed. Results: A majority of the mutations affected either the Mut L homologue (MLH) 1 (n = 75) or the Mut S homologue (MSH) 2 (n = 48) and were quite evenly distributed, with some clustering in MSH2 exon 12 and MLH1 exon 16. Most MSH2 mutations consisted of frameshift (60%) or nonsense changes (23%), whereas MLH1 was mainly affected by frameshift (40%) or missense alterations (31%). Although most mutations were unique, a few common recurring mutations were identified, Of the families studied (n = 202), 82% met the Amsterdam criteria and 15% did not; the general mutation profile was similar in both groups. Conclusions: The construction of mutation profiles will facilitate the development of diagnostic strategies in HNPCC.