Diffuse Large B Cell Lymphoma Shows Distinct Methylation Profiles of the Tumor Suppressor Genes among the Non-Hodgkin's Lymphomas.

Abstract

BACKGROUND: Aberrant methylation of CpG islands in promoter regions is one of the major mechanisms for silencing of tumor suppressor genes in various types of human cancers including non-Hodgkin's lymphomas (NHL). In this study, we investigated the aberrant promoter methylation status of known or suspected tumor suppressor genes in NHLs and compared the methylation profiles between B-cell and T/NK-cell NHLs. METHODS: 54 cases of B-cell NHLs and 16 cases of T/NK-cell NHLs were examined for the methylation status of eight genes using methylation specific PCR. RESULTS: CpG islands methylation was variously found in eight genes as follows; DAPK (71%), MT1G (70%), p16 (53%), CDH1 (53%), THBS1 (56%), MGMT (27.1%), COX2 (13%), and RUNX3 (11.4%). In six cases (8 %), methylation was not observed in any of these genes. Overall methylation index of B-cell NHLs (0.48) was significantly higher than that of T/NK-cell NHLs (0.32). Of eight genes tested, THBS1 and CDH1 methylations were much more prominent in diffuse large B-cell lymphomas than in T/NK-cell NHLs or other B-cell NHLs. CONCLUSION: This study suggests that aberrant CpG island methylation is a frequent event in NHLs, and diffuse large B-cell lymphomas show overlapping but distinct methylation profiles.