O6-methylguanine-DNA methyltransferase methylation and TP53 mutation in malignant astrocytomas and their relationships with clinical course.

摘要: Epigenetic silencing of O(6)-methylguanine-DNA methyltransferase (MGMT) by promoter methylation can confer cancer cells with an increased sensitivity to alkylating chemotherapeutic agents and a higher susceptibility TP53 transition mutations. The aim our study was assess the correlation MGMT gene mutations clinical characteristics malignant astrocytomas. We analyzed in 45 astrocytomas (16 anaplastic 29 glioblastomas multiforme) treated prospectively 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-2(2-chloroethyl)-3-nitrosourea, interferon-beta radiation therapy, evaluated their usefulness. found 17 (38%) newly diagnosed A clear trend existed between G:C A:T (p = 0.0596). Patients MGMT-methylated tumors displayed greater chance responding adjuvant therapy as compared those MGMT-unmethylated 0.0393). mutation not significantly associated response 0.1310). While neither nor had significant effect on prognosis whole population, presence emerged predictor longer survival when exclusively analyzing patients multiforme. These findings highlight importance specific predictive factor for responsiveness nitrosourea chemotherapy.