Aberrant Promoter Methylation Profile in Low and High Grade Gastric Lymphomas

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.