hMLH1和hMSH2基因在胃癌易感人群中的突变  

hMLH1 and hMSH2 gene mutations in a population susceptible to gastric cancer

作　　者：李建华[1] 吕申[2] 石先哲[3] 刘敏[2] 王彦[2] 

机构地区：[1]大连大学附属中山医院病理科,辽宁省大连市116001 [2]大连医科大学附属第二医院实验中心分子生物学实验室,辽宁省大连市116027 [3]中国科学院大连化学物理研究所国家色谱研究分析中心,辽宁省大连市116011

出　　处：《世界华人消化杂志》2010年第11期1121-1126,共6页World Chinese Journal of Digestology

摘　　要：目的:分析中国北方地区胃癌家系人群及胃癌散发患者hMLH1和hMSH2基因的突变.方法:收集胃癌家族史的胃癌患者16例及5个家系健康人114例,无胃癌家族史的胃癌患者56例,正常人群对照100例.采取外周血,用小样本血液DNA提取试剂盒提取DNA.分别扩增hMLH1的外显子3、8、12、13和外显子16以及hMSH2的外显子5和外显子7,热变性后,用毛细管电泳进行单链构象多态性的分析,对可疑样本进行测序.结果:突变出现在hMLH1基因第8、第12和第16外显子,而外显子3和外显子13没有检测到突变,hMSH2基因的外显子5和外显子7也没有检测到突变.在有家族史的胃癌患者的16例外周血标本中,有6例出现突变,突变率37%;无胃癌家族史的56例患者,总计6例出现突变,突变率11%;胃癌家系健康人群的114例样本中,31例出现突变,突变率27%;在100例对照样本中,5例出现突变,突变率5%.第8外显子的突变点位于219位密码子的第一个碱基(ATC→GTC);第12外显子的突变点位于第384位密码子的第二个碱基(GTT→GAT);第16外显子的突变点位于第553位密码子的第二个碱基(AGT→AGG),这三个突变都是碱基置换.但有家族史的胃癌患者和胃癌家系健康成员的突变率明显高于对照组(P=0.001,0.000),无家族史的胃癌患者突变率虽然略高于对照组,但差异不显著(P=0.204).第16外显子的突变是目前尚未见报道的新的突变.结论:胃癌家系人群体细胞存在与遗传性非息肉性结肠癌(hereditary nonpolyposis colorectal cancer,HNPCC)相似的基因突变.AIM： To analyze human mutL homolog 1 （hMLH1） and hMSH2 gene mutations in Chinese familial gastric cancer kindreds and sporadic gastric cancer patients. METHODS： Blood samples from 16 gastric cancer patients and 114 healthy members with familial clustering of gastric cancer and 56 sporadic gastric cancer patients were collected. After DNA extraction, the fragments of exons 3, 8, 12, 13 and 16 of the hMLH1 gene and exons 5 and 7 of the hMSH2 gene were amplified by polymerase chain reaction （PCR）, followed by single-stranded conformation polymorphism/ capillary electrophoresis （SSCP-CE） genotyping assay. The fragments suspected to harbor mutations were sequenced. RESULTS： Mutations were detected in exon 8, 12 and 16 of the hMLH1 gene, whereas no mutation was detected in exons 5 and 7 of the hMSH2 gene. In subjects with familial clustering of gastric cancer, the mutation frequency was 37% （6/16） in gastric cancer patients and 27% （31/114） in healthy members, both significantly higher than that in controls （5%; P = 0.001 and 0.000, respectively）. The mutation frequency was 11% in gastric patients without familial clustering, significantly lower than that in subjects with familial clustering. The mutation at codon 219 in exon 8 of the hMLH1 gene （A→G） results in a conversion of Ile→Val （ATC→GTC）, whereas the mutation at codon 384 in exon 12 of the hMLH1 gene （T→A） results in a conversion of Asp→ Val （GTT→GAT）. The mutation at codon 553 in exon 16 of the hMLH1 gene （T→G） results in a conversion of Ser→Arg （AGT→AGG）, which represents a novel mutation of the hMLH1 gene that has not been reported before. CONCLUSION： Familial gastric cancer kindreds may have similar hMLH1 gene mutations to those observed in hereditary nonpolyposis colorectal carcinoma.

关 键 词：胃癌 家系 错配修复 基因突变 

分 类 号：R735.2[医药卫生—肿瘤]