O-6-METHYLGUANINE-DNA METHYLTRANSFERASE PROTEIN-LEVELS IN PEDIATRIC BRAIN-TUMORS

Chloroethylnitrosoureas (CENUs) are commonly used in the treatment of pediatric and adult central nervous system (CNS) tumors. The antitumor activity of CENUs has been hypothesized to be due to an alkylation oc curring at the O-6-position of guanine in DNA. The DNA repair protein O-6-methylguanine-DNA methyltransferase (MGMT) is responsible for the repair of these potentially cytotoxic lesions and may underlie tumor r esistance to CENUs. The current study is the largest report of MGMT le vels among newly diagnosed pediatric CNS tumors and the only study tha t has quantitated MGMT by both biochemical and Western immunoblot assa ys. Our results show a good correlation between the two methods (r = 0 .66). Medulloblastoma/primitive neuroectodermal tumor and ependymoma h ad the highest level of MGMT, followed by high-grade glioma and low-gr ade glioma, These data may provide a guide to the use of CENUs in the treatment of pediatric CNS tumors.