J Korean Med Sci.  2005 Apr;20(2):236-241. 10.3346/jkms.2005.20.2.236.

DNA Hypermethylation of Tumor-Related Genes in Gastric Carcinoma

• Hong SH
• Kim HG
• Chung WB
• Kim EY
• Lee JY
• Yoon SM
• Kwon JG
• Sohn YK
• Kwak EK
• Kim JW

• KMID: 1095197
• DOI: http://doi.org/10.3346/jkms.2005.20.2.236

Abstract

The hypermethylation of the CpG islands is a common mechanism for the inactivation of tumor-related genes. In the present study, we analyzed the methylation status of genes for cell repair such as hMLH1, MGMT, and GSTP1, and a gastric cancer-specifically methylated DNA fragment, MINT 25 in gastric cancer cases and control groups. The study population consisted of 100 gastric cancer patients (50 distal and 50 proximal carcinomas), and 238 healthy controls. All genes showed more frequent hypermethylation in the cases than in the control group (p<0.0001). We investigated the association between promoter hypermethylation and relevant parameters including age, gender, alcohol consumption, smoking, and family history. There was a common hypermethylation of hMLH1 (p=0.008), MGMT (p= 0.0001), and GSTP1 (p=0.0003) in females. This study also demonstrates that hypermethylation was strongly associated with non-drinkers (MGMT, p=0.046 and MINT 25, p=0.049) and non-smokers (hMLH1, p=0.044; MGMT, p=0.0003; MINT 25, p=0.029). Moreover, the frequency of MINT 25 hypermethylation increased with age (p=0.037), and MGMT methylation was frequently detected in distal gastric cancer than in proximal type (p=0.038). Our study suggested that promoter hypermethylation of the genes involved in cell repair system and MINT 25 is associated strongly with some subgroups of primary gastric carcinoma.

Keyword

Stomach Neoplasms; DNA Methylation; MLH1 Protein, mammalian; O(6)-Methylguanine-DNA Methyltransferase; Glutathione S-transferase pi; MINT 25

MeSH Terms

Adult
Aged
*DNA Methylation
Female
Glutathione Transferase/genetics
Humans
Isoenzymes/genetics
Male
Middle Aged
Neoplasm Proteins/genetics
Nuclear Proteins/genetics
O(6)-Methylguanine-DNA Methyltransferase/genetics
Promoter Regions (Genetics)
Research Support, Non-U.S. Gov't
Stomach Neoplasms/*genetics

Figure

• 

  Fig. 1 Methylation analysis in gastric cancer. (A) hMLH1, (B) MGMT, and (C) GSTP1 methylation were analyzed by methylation-specific PCR. The presence of visible PCR products in those lanes marked U indicate the presence of unmethylated genes; the presence of products in those lanes marked M indicate the presence of methylated genes. Cases 9, 35, 59, and 92 show methylated and unmethylated bands because of the heterogeneously methylated genes, and cases 5 and 75 do not have methylated genes. (D) MINT 25 methylation analysis was performed by bisulfite-PCR and restriction digestion. Only methylated alleles will be digested by restriction enzymes, and they are indicated by arrows. Case 27 and 28 have homogeneously and, heterogeneously methylated MINT 25 DNA fragments, respectively.

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