Gastric Cancer
Copyright ©The Author(s) 2003. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 15, 2003; 9(1): 26-29
Published online Jan 15, 2003. doi: 10.3748/wjg.v9.i1.26
Silencing-specific methylation and single nucleotide polymorphism of hMLH1 promoter in gastric carcinomas
Da-Jun Deng, Jin Zhou, Bu-Dong Zhu, Jia-Fu Ji, Jeffrey C Harper, Steven M Powell
Da-Jun Deng, Jin Zhou, Bu-Dong Zhu, Jia-Fu Ji, Peking University Health Science Center and Beijing Institute for Cancer Research, Beijing 100034, China
Jeffrey C Harper, Steven M Powell, University of Virginia Health Science Center, Charlottesville, VA 22908-0708, United States
Author contributions: All authors contributed equally to the work.
Supported by grant (2000-A-29) from Peking University Center for Human Disease Genomics, grant (0106) from Peking University Cancer Research Center, grant (3171045) from National Natural Science Foundation of China, and by NIH Grant CA67900
Correspondence to: Professor Da-Jun Deng, Department of Cancer Etiology, Peking University School of Oncology and BICR, Da-Hong-Luo-Chang Street, Western District, Beijing 100034, China.
Telephone: +86-10-66162978 Fax: +86-10-66175832
Received: September 13, 2002
Revised: September 25, 2002
Accepted: October 18, 2002
Published online: January 15, 2003

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), 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.

RESULTS: (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.

CONCLUSION: 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.

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