DNA Methylation Profiles of MGMT, DAPK1, hMLH1, CDH1, SHP1, and HIC1 in B-Cell Lymphomas

ABSTRACT

BACKGROUND: This study was designed to examine the prevalence of aberrant promoter methylation in a selected panel of genes potentially involved in lymphoid tumors. METHODS: The promoter hypermethylation status of MGMT, DAPK1, hMLH1, CDH1, SHP1, and HIC1 was measured by methylation-specific PCR for 82 cases of B-cell lymphoma. Immunohistochemical staining using MGMT and SHP1 antibodies was conducted on 43 out of 82 cases. RESULTS: The number of MGMT aberrant methylations was lower in diffuse large B-cell lymphoma (DLBCL) than in other malignant lymphomas. The methylation of DAPK1 was frequently detected in follicular lymphoma (FL), marginal zone B-cell lymphoma (MZL) and DLBCL. With one exception, methylation of hMLH1 was not observed in B-cell lymphomas. The methylation frequency of CDH1, and HIC1 was similar in B-cell lymphomas. However, the methylation of SHP1 gene was more frequently observed in cases of FL, DLBCL, and MZL than in chronic lymphocytic lymphoma. MGMT and SHP1 promoter methylation were inversely correlated with the protein expression observed upon immunohistochemical staining. CONCLUSIONS: Aberrant promoter methylation of multiple genes occurs with variable frequency throughout the B-cell lymphomas, and methylation of hMLH1 is rarely observed in B-cell lymphomas.