The good, the bad and the ugly: Epigenetic mechanisms in glioblastoma

Cell type-specific patterns of gene expression reflect epigenetic changes imposed through a particular developmental lineage as well as those triggered by environmental cues within adult tissues. There is great interest in elucidating the molecular basis and functional importance of epigenetic mechanisms in both normal physiology and disease – particularly in cancer, where abnormal ‘-omic’ states are often observed. In this article we review recent progress in studies of epigenetic mechanisms in the most common primary adult brain cancer, glioblastoma multiforme. Three distinct areas are discussed. First, the evidence in support of ongoing ‘normal’ epigenetic processes associated with differentiation – as predicted by ‘cancer stem cell’ models of the disease. Second, identification of site-specific and global epigenetic abnormalities. Third, genetic disruptions directly within the core epigenetic machinery, exemplified by the recently identified mutations within isocitrate dehydrogenase genes IDH1/2 and variant histone genes H3.3/H3F3A. These constitute the ‘good, the bad and the ugly’ of epigenetic mechanisms in cancer.