Aberrant Promoter Methylation Profile in Low and High Grade Gastric Lymphomas.
- Author:
Jae Kyun JU
1
;
Hyoung Soo KIM
;
Yang Suk KOH
;
Jung Chul KIM
;
Young Kyu PARK
;
Seong Yeob RYU
;
Heong Rok KIM
;
Dong Yi KIM
;
Young Jin KIM
;
Shin Kon KIM
;
Jae Hyuk LEE
Author Information
1. Department of Surgery, Chonnam National University Medical School, Gwangju, Korea.
- Publication Type:Original Article
- Keywords:
Stomach;
Lymphoma;
Methylation
- MeSH:
Apoptosis;
Carcinogenesis;
Cell Cycle Checkpoints;
CpG Islands;
DNA Mismatch Repair;
Epigenomics;
Gastric Mucosa;
Helicobacter pylori;
Jeollanam-do;
Lymphoid Tissue;
Lymphoma*;
Lymphoma, B-Cell;
Lymphoma, B-Cell, Marginal Zone;
Lymphoma, Non-Hodgkin;
Methylation*;
Phenotype;
Polymerase Chain Reaction;
Protein Kinases;
Stomach
- From:Journal of the Korean Surgical Society
2005;69(2):120-128
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: Malignant lymphoma arising from mucosa-associated lymphoid tissue (MALT) accounts for a large proportion of a extranodal lymphomas. The stomach is the preferential site of MALT lymphoma, and the pathogenesis of a gastric MALT lymphoma is known to be closely related to Helicobacter pylori infection. Epigenetic silencing of tumor- related genes due to CpG island methylation, has recently been reported in B cell lymphomas, but its role in gastric lymphomas is unclear. METHODS: We analyzed the methylation status of cell cycle control (p16), apoptosis regulation (Death-associated protein kinase, DAPK) and DNA mismatch repair (MGMT, hMLH1, and hMSH3) genes using a methylation-specific polymerase chain reaction in 46 low- and high-grade gastric lymphomas, pathologically documented at Chonnam National University Hospital, between January 1999 and August 2004. RESULTS: Methylation of p16, DAPK, and MGMT was more frequent in the high- than in the low-grade lymphomas (80, 80 and 93 vs. 71, 74 and 84%, respectively). Methylation of hMLH1 and hMSH3 was rare or absent. There was no difference in frequencies of CIMP between the low- and high-grade gastric lymphomas. Of the 46 gastric lymphoma cases, compared with matched normal gastric mucosa, five had an MSI-low phenotype, with two and three in the low- and high-grade lymphomas, respectively. CONCLUSION: Methylation of p16, DAPK, and MGMT may represent a major pathogenetic event in gastric lymphomas, which may contribute to the early tumorigenesis and have clinical applications in the management and follow-up of low and high grade gastric lymphomas.
