CpG island methylation of the MLH1, MGMT, DAPK, and CASP8 genes in cancerous and adjacent noncancerous stomach tissues

Medicina (Kaunas). 2013;49(8):361-6.

Abstract

BACKGROUND AND OBJECTIVE. Many factors are involved in the development of gastric adenocarcinoma. The CpG island methylation of apoptosis and mismatch repair genes by the loss of their function is important in gastric adenocarcinoma. The aim of this study was to determine the methylation frequency of MLH1, MGMT, CASP8, and DAPK in cancerous and adjacent noncancerous stomach tissues, to determine possible associations with the selected clinicopathological characteristics, and to identify possible correlation between the methylation of individual genes. MATERIAL AND METHODS. The methylation status of MLH1, MGMT, DAPK, and CASP8 was investigated in 69 patients with gastric adenocarcinoma by using methylation-specific polymerase chain reaction. The associations between patients' clinical characteristics and methylation status were assessed. RESULTS. The methylation frequency of the MLH1, DAPK, MGMT, and CASP8 gene promoters in cancerous and adjacent noncancerous tissues was 31.9% and 27.5%; 47.8% and 46.4%; 36.2% and 44.9%; and 5.8% and 5.8%, respectively, but the differences were not significant. There was no significant association between the methylation status of the mentioned genes and clinicopathological characteristics, such as age, sex, tumor type by the Lauren classification, degree of differentiation G, and TNM staging. An inverse correlation between the methylation of the DAPK and MLH1 gene promoters in cancerous and surrounding noncancerous tissues was found. CONCLUSIONS. The methylation of the MLH1, MGMT, DAPK, and CASP8 genes was found to occur both in cancerous and noncancerous stomach tissues. These findings provide additional insights into gene methylation patterns in gastric adenocarcinoma.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adenocarcinoma / genetics*
  • Adult
  • Aged
  • Aged, 80 and over
  • Caspase 8 / genetics*
  • CpG Islands
  • DNA Methylation*
  • DNA Modification Methylases / genetics*
  • DNA Repair Enzymes / genetics*
  • Death-Associated Protein Kinases / genetics*
  • Epigenesis, Genetic
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Middle Aged
  • MutL Protein Homolog 1
  • Nuclear Proteins / genetics*
  • Promoter Regions, Genetic
  • Stomach Neoplasms / genetics*
  • Tumor Suppressor Proteins / genetics*
  • Young Adult

Substances

  • Adaptor Proteins, Signal Transducing
  • MLH1 protein, human
  • Nuclear Proteins
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • DAPK1 protein, human
  • Death-Associated Protein Kinases
  • CASP8 protein, human
  • Caspase 8
  • MutL Protein Homolog 1
  • DNA Repair Enzymes