Distinct TPEF/HPP1 gene methylation patterns in gastric cancer indicate a field effect in gastric carcinogenesis

Dig Liver Dis. 2008 Dec;40(12):920-6. doi: 10.1016/j.dld.2008.05.004. Epub 2008 Sep 16.

Abstract

Background: Aberrant methylation of the transmembrane protein containing epidermal growth factor and folistatin domains/hyperplastic polyposis 1 gene was recently reported in hyperplastic colon polyps, colorectal adenomas and carcinomas. However, there are only limited data on significance of transmembrane protein containing epidermal growth factor and folistatin domains/hyperplastic polyposis 1 gene methylation in gastric adenocarcinomas.

Aim: The aim of this study was to determine the prevalence of transmembrane protein containing epidermal growth factor and folistatin domains/hyperplastic polyposis 1 promoter methylation in gastric adenocarcinomas.

Patients: Study population consists of 48 patients with gastric cancer and 11 dyspeptic patients.

Methods: Using the Methylight assay, transmembrane protein containing epidermal growth factor and folistatin domains/hyperplastic polyposis 1 gene methylation was assessed in fresh frozen cancer tissue and matched tumoural-free area of patients with gastric cancer and in the gastric mucosa of dyspeptic patients.

Results: Transmembrane protein containing epidermal growth factor and folistatin domains/hyperplastic polyposis 1 promoter gene methylation was observed in 35 of 48 (73%) gastric adenocarcinomas, and in 27 of 48 (56%) matched tumoural-free area cases (p=0.087). In contrast, the occurrence of transmembrane protein containing epidermal growth factor and folistatin domains/hyperplastic polyposis 1 methylation was much lower in gastric mucosa of dyspeptics (1 of 11; 9%) and the difference was significant in comparison with both tumoural tissue (p=0.0001) and tumoural-free area (p=0.0047) of cancer patients. Transmembrane protein containing epidermal growth factor and folistatin domains/hyperplastic polyposis 1 gene expression was significantly reduced in adenocarcinomas in comparison with matched tumoural-free area (p=0.022).

Conclusion: Our data suggest that methylation of transmembrane protein containing epidermal growth factor and folistatin domains/hyperplastic polyposis 1 is present in the majority of gastric adenocarcinomas and in the surrounding tumoural-free area, indicating that this epigenetic change may point to a field effect in the gastric mucosa.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • DNA Methylation / genetics*
  • Dyspepsia / genetics
  • Female
  • Gastric Mucosa
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Promoter Regions, Genetic / genetics*
  • Stomach Neoplasms / genetics*

Substances

  • Membrane Proteins
  • Neoplasm Proteins
  • TMEFF2 protein, human