The DNA methylome of glioblastoma multiforme

Glioblastoma multiforme (GBM) is the most frequent brain tumor in adults. This lethal cancer is a challenge in neuro-oncology since patients almost invariably succumb to the disease. Intensive molecular studies have revealed a variety of deregulated genetic pathways involved in DNA repair, apoptosis, cell migration, angiogenesis and cell cycle. Recent investigation of epigenetic lesions in GBM have led to a more comprehensive understanding of this malignancy and even to target therapies, including the milestone of temozolomide chemotherapy, which makes possible a better outcome for GBM patients with hypermethylated MGMT. Nevertheless, the whole scenario including global hypomethylation, aberrant promoter hypermethylation, histone modification and chromatin states in GBM has only been partially revealed. We discuss the magnitude of epigenetic alterations in the pathogenesis of GBM and their translational relevance to patient survival. (C) 2010 Elsevier Inc. All rights reserved.