Aberrantly methylated MGMT, hMLH1 and hMSH2 in tumor and serum DNA of gliomas patients

Abstract

OBJECTIVE This study is to investigate the prevalence of promoter CpG island methylation of O6-methylguananine-DNA methyltransferase (MGMT), mismatch repair genes ( hMLH1 and hMSH2) in both tumor and serum samples of gliomas. METHODS Methylation-specific PCR (MSP) was employed to detect promoter CpG island methylation of the MGMT, hMLH1 and hMSH2 genes in 39 samples taken from surgery and 32 samples of pretreatment serum all from the patients with gliomas. RESULTS Promoter CpG island methylation of MGMT, hMLH1 and hMSH2 was detected and the results were 46.2%, 10.3% and 20.5%, respectively in tumor DNA of the cases with gliomas, and 40.6%, 9.4% and 18.8%, respectively in serum DNA of the cases. The methylation pa Ĵ ern in primary tumor and serum was found to be concordant in matched tissue and serum samples of 21 patients. In the cases with positive result of methylation for MGMT, hMLH1 and hMSH2 in tumor tissues, the results of detection for those in the paired serum sample were 77.8% (7/9), 66.7% (2/3) and 75.0 % (3/4), respectively. False positive results were not obtained in any of the patients who did not exhibit methylation. No association was found between the promoter methylation of MGMT, hMLH1, and hMSH2 genes in primary gliomas and gender, age, localization, grade of malignant or tumor stage. CONCLUSION Promoter CpG island methylation is a frequent event in gliomagenesis. Methylation analysis appears to be a promising predictive factor of the prognosis for the glioma patients treated with alkylating drugs and a noninvasive tumor marker in serum DNA.