Methylation profiling of the DNA repair genes in glioblastoma multiforme and its clinical relevance

1572 Background: Alterations of DNA repair protein have been associated with sensitivity to anticancer drugs, and transcriptional repression by promoter hypermethylation is an essential role in the protein inactivation. Recently methylation of the O6-methylguanine-DNA methyltransferase (MGMT) promoter is an expected predictor not only of responsiveness to chemotherapy but also of prognosis of patient with glioma. The aim of this study was to investigate the methylation profile in DNA repair genes, MGMT, FANCF and hMLH1, of glioblastoma multiforme and correlation between the methylation status and outcome of the patients. Methods: In 40 adult patients with glioblastoma multiforme treated with surgery, irradiation, and/or chemotherapy (ACNU: n=19, cisplatin: n=11), median age at diagnosis was 55 years old, and median overall survival time was 14 months. Promoter hypermethylation of MGMT, hMLH1 and FANCF genes in tumor DNA was examined using the methylation-specific PCR assay and COBRA (combined bisulfite restriction analysis) method. We analyzed relation between methylation status of the MGMT promoter and survival in these patients. Results: The hypermethylation in MGMT, FANCF and hMLH1 promoter were detected 24 of 40 (60%), 1 of 40 (2.5%), and 0 of 40, respectively. Kaplan-Meier analysis and log-rank test revealed no significant difference in overall survival between patient subgroups divided by methylation status of MGMT promoter. Cox proportional hazard regression analysis adjusted for age of onset and extent of surgical resection showed the MGMT promoter hypermethylation had no significant association with overall survival time. Conclusions: In our series, promoter hypermethylation of MGMT was not a predictive factor for outcome, however, more controlled study would be required to validate this result. And it is still suggested epigenetic alteration of MGMT might influence nature of glioblastoma compared with other DNA repair genes. No significant financial relationships to disclose.