Promoter hypermethylation of O6-methylguanine-DNA methyltransferase gene in cholangiocarcinoma.

Objective O6-methylguanineDNA methyltransferase (MGMT) is an effective DNA repair enzyme. The aberrant methylation of its promoter region CpG islands may be one of the important mechanisms of carcinogenesis. We studied the methylation status of MGMT gene and clinical significance in cholangiocarcinoma. Methods Target DNA was modified by sodium bisulfite, coverting all unmethylated, but not methylated, cytosines to uracil. Then, the promoter hypermethylation of MGMT gene and the expression of MGMT protein were detected by methylation-specific PCR and immunohistochemical staining. Results Aberrant methylation of MGMT gene was detected in 17 of 36(47. 2%) in cholangiocarcinoma tissues. 21 cases showed negative immunoreactivities of MGMT protein. Among them, there were 14 cases with aberrant methylation of MGMT gene. 15 cases showed positive immunoreactivities of MGMT protein, but only 3 cases with aberrant methylation of MGMT gene. There were statistically differences in the exent of differentiation, invasion and the MGMT protein expression between the methylated tissues and those unmethylated but not in pathologic type and lymph node metastasis. Conclusion Hypermethylation of the MGMT promoter is a frequency molecular event in cholangiocarcinoma and might be involved in carcinogenesis. The methylation status of MGMT gene may be helpful to predict prognosis in patients with cholangiocarcinoma.