O6-Methylguanine-DNA Methyltransferase-deficient Phenotype in Human Gliomas: Frequency and Time to Tumor Progression after Alkylating Agent-based Chemotherapy

The DNA repair protein O 6 -methylguanine-DNA methyltransferase (MGMT) contributes to the resistance of human brain tumor cell lines and xenografts to methylating and chloroethylating agents. We assayed MGMT in 174 newly diagnosed or recurrent gliomas to ( a ) quantitate changes in MGMT activity associated with alkylating agent-based chemotherapy; and ( b ) assess the contribution of MGMT to clinical outcome. Glioma MGMT activity ranged 300-fold, averaging 3,800 ± 7,200 molecules/cell. Twenty-four percent of tumors lacked detectable activity [Methyl repair-deficient (Mer − ) phenotype, defined here as