Alterations and hypermethylation of the p14(ARF) gene in gastric cancer

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Updated: Oct 15, 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

S Iida1, Y Akiyama, T Nakajima

  • 1Second Department of Surgery, Tokyo Medical and Dental University School of Medicine, Tokyo, Japan.

International Journal of Cancer
|August 5, 2000
PubMed

Insights

The p14(ARF) gene, a growth suppressor, is frequently inactivated in diffuse-type gastric cancer cell lines through homozygous deletion or methylation. This suggests p14(ARF) alterations play a role in diffuse-type gastric carcinogenesis.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • The p14(ARF) gene, a product of alternative splicing from the p16(INK4a) locus, functions as a critical growth suppressor.
  • Gastric cancer is a significant global health concern, with distinct subtypes like diffuse-type and intestinal-type.

Purpose of the Study:

  • To investigate the alterations of the p14(ARF) gene in gastric cancer cell lines and primary tumors.
  • To determine the frequency of p14(ARF) gene inactivation in diffuse-type versus intestinal-type gastric cancers.

Main Methods:

  • Analysis of mRNA expression, homozygous deletion, mutation, and promoter methylation of the p14(ARF) gene in 11 gastric cancer cell lines.
  • Examination of p14(ARF) promoter methylation status in 62 primary gastric cancer samples.

Main Results:

  • No p14(ARF) mRNA expression was observed in 5 out of 7 diffuse-type gastric cancer cell lines.
  • Homozygous deletion and promoter methylation were identified as mechanisms of p14(ARF) inactivation in diffuse-type cell lines.
  • p14(ARF) inactivation was significantly more frequent in diffuse-type gastric cancer cell lines (71.4%) compared to intestinal-type (0%).
  • Promoter methylation of p14(ARF) showed a higher frequency in primary diffuse-type gastric cancers (45.5%) than in intestinal-type (25%).

Conclusions:

  • The p14(ARF) gene is frequently inactivated by homozygous deletion or methylation in diffuse-type gastric cancer.
  • These findings suggest a potential role for p14(ARF) alterations in the development of diffuse-type gastric cancer.

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