Molecular subtypes, stem cells and heterogeneity: Implications for personalised therapy in glioma

We discuss a number of recent developments that have led to new concepts regarding the biology of gliomas. Collective tissue banking, large-scale genomic, transcriptomic and methylomic expression profiling, and discoveries such as isocitrate dehydrogenase gene mutation and the C-phosphate-G island methylation phenotype have improved glioma classification schemes. Furthermore, the discovery of glioma stem cells has both enhanced and complicated our understanding. Gene signatures describing a proneural versus mesenchymal subtype within glioblastoma multiforme is reflected in both parental tumour as well as glioma stem cells and correlates with differential prognosis and response to radiation and chemotherapy. Finally, we discuss how these factors integrate with the known heterogeneity within brain cancers and the implications of this for the development of personalised therapy.