Gliomas are the most common malignant primary brain tumors, of which 
glioblastoma is the most malignant form (WHO grade IV), and notorious for 
treatment resistance. Over the last decade mutations in epigenetic regulator 
genes have been identified as key drivers of subtypes of gliomas with distinct 
clinical features. Most characteristic are mutations in IDH1 or IDH2 in lower 
grade gliomas, and histone 3 mutations in pediatric high grade gliomas that are 
also associated with characteristic DNA methylation patterns. Furthermore, in 
adult glioblastoma patients epigenetic silencing of the DNA repair gene MGMT by 
promoter methylation is predictive for benefit from alkylating agent therapy. 
These epigenetic alterations are used as biomarkers and play a central role for 
classification of gliomas (WHO 2016) and treatment decisions. Here we review the 
pivotal role of epigenetic alterations in the etiology and biology of gliomas. 
We summarize the complex interactions between "driver" mutations, DNA 
methylation, histone post-translational modifications, and overall chromatin 
organization, and how they inform current efforts of testing epigenetic 
compounds and combinations in preclinical and clinical studies.