Mismatch repair genes in Lynch syndrome: a review
Mismatch repair genes in Lynch syndrome: a review
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DOI：
10.1590/s1516-31802009000100010
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发表时间：
2009-01-01
影响因子：
1.4
通讯作者：
Rossi, Benedito Mauro
中科院分区：
文献类型：
--
作者：
Silva, Felipe Cavalcanti Carneiro da;Valentin, Mev Dominguez;Rossi, Benedito Mauro
Lynch综合征占所有结直肠癌病例的1-7%，是由脱氧核糖核酸（DNA）错配修复基因的种系突变引起的常染色体显性遗传性癌症易感综合征。自从发现具有DNA错配修复功能的主要人类基因以来，其中五个基因的突变与Lynch综合征的易感性相关：mutS同源物2（MSH 2）; mutt。同源物1（MLH 1）; mutS同源物6（MSH 6）;减数分裂后分离增加2（PMS 2）;和减数分裂后分离增加1（PMS 1）。已经提出一个额外的错配修复基因，mutt。同源物3（MLH 3）也在Lynch综合征易感性中起作用，但该基因突变的临床意义尚不清楚。根据InSIGHT数据库（国际胃肠遗传性肿瘤学会），已知约500种不同的LS相关错配修复基因突变，主要涉及MLH 1（50%）和MSH 2（40%），其他占10%。在理解Lynch综合征的分子基础方面已经取得了很大进展。分子表征将是定义Lynch综合征的最准确的方法，并将提供关于结肠和结肠外癌症风险的更准确的预测信息，并实现最佳的癌症监测方案。
Lynch syndrome represents 1-7% of all cases of colorectal cancer and is an autosomal-dominant inherited cancer predisposition syndrome caused by germline mutations in deoxyribonucleic acid (DNA) mismatch repair genes. Since the discovery of the major human genes with DNA mismatch repair function, mutations in five of them have been correlated with susceptibility to Lynch syndrome: mutS homolog 2 (MSH2); mutt. homolog 1 (MLH1); mutS homolog 6 (MSH6); postmeiotic segregation increased 2 (PMS2); and postmeotic segregation increased 1 (PMS1). It has been proposed that one additional mismatch repair gene, mutt. homolog 3 (MLH3), also plays a role in Lynch syndrome predisposition, but the clinical significance of mutations in this gene is less clear. According to the InSiGHT database (International Society for Gastrointestinal Hereditary Tumors), approximately 500 different LS-associated mismatch repair gene mutations are known, primarily involving MLH1 (50%) and MSH2 (40%), while others account for 10%. Much progress has been made in understanding the molecular basis of Lynch Syndrome. Molecular characterization will be the most accurate way of defining Lynch syndrome and will provide predictive information of greater accuracy regarding the risks of colon and extracolonic cancer and enable optimal cancer surveillance regimens.