Aberrations of the Epigenome in Gliomas: Novel Targets for Therapy
Abstract Aberrations in the epigenetic machinery of the genome result in inactivation of critical genes and are important mechanisms in the evolution of malignancies that not only contributes to tumorigenesis but may also precede genetic changes. Several such epigenetic mechanisms have been observed in gliomas including DNA hypermethylation at the promoter or the coding regions of genes, histone modifications including methylation and acetylation, nucleosomal rearrangement, and dysregulation of noncoding RNA expression; these changes have been shown to play a critical role in the biology of gliomas and to contribute to the clinical outcome. This review examines the general role of epigenetic changes in the malignant process and focuses on the known changes in gene expression in gliomas due to epigenetic modifications, both in the context of gliomagenesis and in the development of new therapeutic strategies against these malignancies.
KeywordsEpigenetic machinery Glioma Histone modifications New therapeutics
- Galanis EJ et al (2007) N047B: NCCTG phase II trial of vorinostat (suberoylanilide hydroxamic acid) in recurrent glioblastoma multiforme (GBM). J Clin Oncol 25Google Scholar
- Marks PA et al (2004) Histone deacetylase inhibitors: Development as cancer therapy. Novartis Found Symp 259:269–281; discussion 281–268Google Scholar
- Wolfgang WW, Weller M, Neurooncology Working Group of the German Cancer Societ (2008). Randomized phase III study of sequential radiochemotherapy of oligoastrocytic tumors of WHO-grade III with PCV or temozolomide: NOA-04. J Clin Oncol 26: May 20 suppl; abstr LBA2007Google Scholar