AIM:To investigate CpG methylation and single nucleotidepolymorphism(SNP)of a specific promoter region of hMLH1in primary gastric carcinoma.METHODS:Primary gastric carcinomas(n=80),theircorresponding normal mucosal samples,and gastric mucosalbiopsies from normal/gastritis control patients(n=54)wereused.Hypermethylation at-253 nt and-251 nt in relationwith the translational start site and SNP of a silencing specificregion(-339 nt-46 nt)in the hMLH1 promoter were analyzedby BstUI-combined bisulfite assay(COBRA),denaturing highperformance liquid chromatogram(DHPLC),and sequencing.RESULTS:(A)The specific methylation at-253 nt and-251nt was observed in 2 of 60 primary gastric carcinomas,butneither in all of the corresponding mucosa nor in normal/gastritis samples,by Bst UI-COBRA and DHPLC.(B)ThehMLH1 promoter was methylated homogeneously in thexenograft of the primary gastric carcinoma with themethylated and unmethylated hMLH1.(C)The pattern ofSNP at-93 nt of the hMLH1 promoter in 54 Chinese patientswith gastric carcinoma was the same as that in the controlpatients:51% was A/G heteroalleles,34% and 15% wereA/A and G/G homoalleles,respectively.CONCLUSION:Biallelic inactivation of hMLH1 by epigeneticsilencing existed in human primary gastric carcinomahomogeneously.Hypermethylation of hMLH1 may play arole in the early stage of development of a few gastriccarcinomas.The SNP at-93 nt is not related to thesusceptibility of gastric carcinomas. AIM: To investigate CpG methylation and single nucleotide polymorphism (SNP) of a specific promoter region of hMLH1 in primary gastric carcinoma. METHODS: Primary gastric carcinomas (n = 80), theircorresponding normal mucosal samples, and gastric mucosal biopsies from normal / gastritis control patients = 54) wereused.Hypermethylation at -253 nt and -251 nt in relationwith the translational start site and SNP of silencing specificregion (-339 nt-46 nt) in the hMLH1 promoter were analyzed by BstUI-combined bisulfite assay (COBRA), denaturing high performance liquid chromatogram (DHPLC), and sequencing .RESULTS: (A) The specific methylation at -255 nt and -251 nt was observed in 2 of 60 primary gastric carcinomas, butneither in all of the corresponding mucosa nor in normal / gastritis samples, by Bth UI-COBRA and DHPLC. (B) The hMLH1 promoter was methylated homogeneously in the xenograft of the primary gastric carcinoma with themethylated and unmethylated hMLH1. (C) The pattern of SNP at-93 nt of the hMLH1 promoter in 54 Chines e patients with gastric carcinoma was the same as that in the controlpatients: 51% was A / G heteroalleles, 34% and 15% were A / A and G / G homoalleles, respectively.CONCLUSION: Biallelic inactivation of hMLH1 by epigeneticsilencing existed in human primary gastric carcinoma homogeneously. Hypermethylation of hMLH1 may play arole in the early stage of development of a few gastric carcinomas. The SNP at-93 nt is not related to the susceptibility of gastric carcinomas.