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Journal of Signal Transduction
Volume 2012 (2012), Article ID 519807, 9 pages
http://dx.doi.org/10.1155/2012/519807
Review Article

Beyond Genetics in Glioma Pathways: The Ever-Increasing Crosstalk between Epigenomic and Genomic Events

Department of Neurosurgery, University of Goettingen, Robert-Koch-Straße 40, 37075 Goettingen, Germany

Received 28 December 2011; Accepted 10 April 2012

Academic Editor: Juan-Carlos Martinez Montero

Copyright © 2012 Ramón Martínez. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Diffuse gliomas are the most frequent brain tumor in adults. This group of brain neoplasms, ranging from histologically benign to aggressive malignant forms, represents a challenge in modern neurooncology because of the diffuse infiltrative growth pattern and the inherent tendency to relapse as a more malignant tumor. Once the disease achieves the stage of glioblastoma multiforme (GBM), the prognosis of patients is dismal and the median survival time is 15 months. Exhaustive genetic analyses have revealed a variety of deregulated genetic pathways involved in DNA repair, apoptosis, cell migration/adhesion, and cell cycle. Recently, investigation of epigenetic alterations in gliomas has contributed to depict the complexity of the molecular lesions leading to these malignancies. Even though, the efficacy of the state-of-the-art form of chemotherapy in malignant gliomas with temozolomide is based on the methylation-associated silencing of the DNA repair gene MGMT. Nevertheless, the whole scenario including global DNA hypomethylation, aberrant promoter hypermethylation, histone modification, chromatin states, and the role of noncoding RNAs in gliomas has only been partially revealed. We discuss the repercussion of epigenetic alterations underlying deregulated molecular pathways in the pathogenesis and evolution of gliomas and their impact on management of patients.