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Updated: Aug 14, 2026

Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
07:50

Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer

Published on: September 18, 2020

Frequent epigenetic silencing of the bone morphogenetic protein 2 gene through methylation in gastric carcinomas

X-Z Wen1, Y Akiyama, S B Baylin

  • 1Department of Molecular Oncology, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.

Oncogene
|November 30, 2005
PubMed

Insights

Bone morphogenetic protein-2 (BMP-2) promoter methylation silences BMP-2 expression in gastric cancer. This epigenetic silencing is linked to carcinogenesis, especially in diffuse-type gastric tumors.

Area of Science:

  • Molecular Biology
  • Oncology
  • Epigenetics

Background:

  • Bone morphogenetic protein-2 (BMP-2) exhibits antiproliferative effects on gastric cells.
  • Loss of BMP-2 expression is observed in various cancers, but the mechanism is unclear.
  • Epigenetic silencing via DNA methylation is a critical factor in cancer development.

Purpose of the Study:

  • To investigate the role of BMP-2 promoter methylation in gastric and colon cancer.
  • To determine the association between BMP-2 methylation and BMP-2 expression in gastric cancer tissues.
  • To explore the potential link between BMP-2 methylation and gastric carcinogenesis, particularly the diffuse type.

Main Methods:

  • Methylation-specific polymerase chain reaction (PCR) was used to analyze BMP-2 promoter methylation in cell lines and tissues.
  • 5-aza-2'-deoxycytidine treatment was employed to assess BMP-2 mRNA activation in methylated cells.
  • Immunohistochemical staining was performed to evaluate BMP-2 protein expression in gastric cancer tissues.

Main Results:

  • CpG island methylation of the BMP-2 promoter was detected in gastric and colon cancer cell lines.
  • BMP-2 mRNA expression was restored upon demethylation treatment.
  • BMP-2 promoter methylation was found in 42.9% of gastric cancer tissues, correlating with reduced BMP-2 protein expression (P = 0.0003).
  • BMP-2 methylation was significantly more prevalent in diffuse-type (60.7%) compared to intestinal-type (25%) gastric carcinomas (P = 0.007).

Conclusions:

  • Aberrant methylation of the BMP-2 promoter leads to the loss of BMP-2 expression in gastric cancer.
  • BMP-2 promoter methylation is strongly associated with reduced BMP-2 protein levels in primary gastric carcinomas.
  • Epigenetic silencing of BMP-2 may contribute to gastric carcinogenesis, with a notable link to the diffuse histological subtype.

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