Aberrantly Methylated MGMT,hMLH1 and hMSH2 in Tumor and Serum DNA of Gliomas Patients

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OBJECTIVE This study is to investigate the prevalence ofpromoter CpG island methylation of O~6-methylguananine-DNAmethyltransferase (MGMT), mismatch repair genes (hMLH1 andhMSH2) in both tumor and serum samples of gliomas.METHODS Methylation-specific PCR (MSP) was employed todetect promoter CpG island methylation of the MGMT, hMLH1and hMSH2 genes in 39 samples taken from surgery and 32samples of pretreatment serum all from the patients with gliomas.RESULTS Promoter CpG island methylation of MGMT, hMLH1and hMSH2 was detected and the results were 46.2%, 10.3% and20.5%, respectively in tumor DNA of the cases with gliomas,and 40.6%, 9.4% and 18.8%, respectively in serum DNA of thecases. The methylation pattern in primary tumor and serum wasfound to be concordant in matched tissue and serum samplesof 21 patients. In the cases with positive result of methylationfor MGMT, hMLH1 and hMSH2 in tumor tissues, the results ofdetection for those in the paired serum sample were 77.8% (7/9),66.7% (2/3) and 75.0 % (3/4), respectively. False positive resultswere not obtained in any of the patients who did not exhibitmethylation. No association was found between the promotermethylation of MGMT, hMLH1, and hMSH2 genes in primarygliomas and gender, age, localization, grade of malignant or tumorstage.CONCLUSION Promoter CpG island methylation is a frequentevent in gliomagenesis. Methylation analysis appears to bea promising predictive factor of the prognosis for the gliomapatients treated with alkylating drugs and a noninvasive tumormarker in serum DNA. OBJECTIVE This study is to investigate the prevalence of promoter CpG island methylation of O ~ 6-methylguananine-DNAmethyltransferase (MGMT), mismatch repair genes (hMLH1 andhMSH2) in both tumor and serum samples of gliomas. METHODS Methylation-specific PCR todetect 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 thecases. The methylation pattern in primary tumor and serum was wound 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 samples were 77.8% (7/9), 66.7% (2/3 ) and 75.0% (3/4), respectively. False positive resultswere not 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 tumorstage. CONCLUSION Promoter CpG island methylation is a frequentevent in gliomagenesis. Methylation analysis appears to bea promising predictive factor of the prognosis for the gliomapatients treated with alkylating drugs and a noninvasive tumor marker in serum DNA.
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