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AIM: To investigate CpG methylation and single nucleotidepolymorphism (SNP) of a specific promoter region of hMLH11in primary gastric carcinoma.METHODS: Primary gastric carcinomas (7＝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 hMLH-1 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 hMLH11. (C) The patt ofSNP at -93 nt of the hMLH11 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 hMLH11 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.