Prognostic significance of O6-methylguanine DNA methyltransferase and p57 methylation in patients with diffuse large B-cell lymphomas

APMIS. 2009 Feb;117(2):87-94. doi: 10.1111/j.1600-0463.2008.00017.x.

Abstract

To evaluate whether promoter methylation is related to responsiveness for chemotherapy or clinical outcome, we performed an association analysis between methylation and clinical outcomes. Patients with nodal diffuse large B-cell lymphomas (DLBCL) at a single institute (n=44) were studied for methylation of tumor-related genes, MGMT, p15(INK4B), p16(INK4A), p16(INK4A), Mad2, TMS1/ASC, CASP8, and GSTP1. The clinical behavior of DLBCL after chemotherapy was followed up and analyzed. Hypermethylation of promoters of MGMT, p15(INK4B), p16(INK4A), p16(INK4A), Mad2, and TMS1/ASC genes was observed in 52.3%, 31.8%, 54.5%, 47.7%, 50%, and 2.3% of the cases, respectively. Methylation of CASP8 and GSTP1 genes was not observed. Promoter methylation was not related to chemo-responsiveness, disease-free survival, and progress of disease after chemotherapy. However, in overall survival analyses, MGMT methylation (p<0.05) and responsiveness to chemotherapy (p<0.01) were significant prognostic factors in patients with DLBCL. In the low-risk group, patients with p57 methylation showed longer overall survival than patients without p57 methylation (p=0.02) and all patients with p57 methylation were alive during follow-up. Our results demonstrate that aberrant promoter methylation of MGMT and p57 is an additional biological marker for predicting increased overall survival in patients with DLBCL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • CpG Islands
  • Cyclin-Dependent Kinase Inhibitor p57 / genetics*
  • DNA Methylation*
  • Humans
  • Lymphoma, Large B-Cell, Diffuse / genetics*
  • Lymphoma, Large B-Cell, Diffuse / mortality*
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Middle Aged
  • O(6)-Methylguanine-DNA Methyltransferase / genetics*
  • Prognosis
  • Promoter Regions, Genetic

Substances

  • CDKN1C protein, human
  • Cyclin-Dependent Kinase Inhibitor p57
  • O(6)-Methylguanine-DNA Methyltransferase