Silencing-specific methylation and single nucleotide polymorphism of hMLH1 promoter in gastric carcinomas

• Published in: World journal of gastroenterology : WJG 2003-01, Vol.9 (1), p.26-29
• Main Authors: Deng, Da-Jun, Zhou, Jin, Zhu, Bu-Dong, Ji, Jia-Fu, Harper, Jeffrey C, Powell, Steven M
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing; Adult; Aged; Aged, 80 and over; Carcinoma - genetics; Carrier Proteins; CpG Islands; DNA Repair; Female; Gastric Cancer; Gene Silencing; Humans; Male; Methylation; Middle Aged; MutL Protein Homolog 1; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Nuclear Proteins; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Stomach Neoplasms - genetics; Sulfites - metabolism
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v9.i1.26

To investigate CpG methylation and single nucleotide polymorphism (SNP) of a specific promoter region of hMLH1 in primary gastric carcinoma. Primary gastric carcinomas (n=80), their corresponding normal mucosal samples, and gastric mucosal biopsies from normal/gastritis control patients (n=54) were used. Hypermethylation at -253 nt and -251 nt in relation with the translational start site and SNP of a silencing specific region (-339 nt-46 nt) in the hMLH1 promoter were analyzed by Bst UI-combined bisulfite assay (COBRA), denaturing high performance liquid chromatogram (DHPLC), and sequencing. (A) The specific methylation at -253 nt and -251 nt was observed in 2 of 60 primary gastric carcinomas, but neither in all of the corresponding mucosa nor in normal/gastritis samples, by Bst UI-COBRA and DHPLC. (B) The hMLH1 promoter was methylated homogeneously in the xenograft of the primary gastric carcinoma with the methylated and unmethylated hMLH1. (C) The pattern of SNP at -93 nt of the hMLH1 promoter in 54 Chinese patients with gastric carcinoma was the same as that in the control patients: 51 % was A/G heteroalleles, 34 % and 15 % were A/A and G/G homoalleles, respectively. Biallelic inactivation of hMLH1 by epigenetic silencing existed in human primary gastric carcinoma homogeneously. Hypermethylation of hMLH1 may play a role 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.