Novel insights into the pathogenesis of gliomas based on large-scale molecular profiling approaches

To review recent advances in brain tumor research based on the application of large-scale molecular profiling approaches, in particular concerning their impact on the understanding of glioma pathogenesis as well as their role in glioma diagnostics and therapy.

The search for new cancer genes as well as the generation of tumor-specific genomic, epigenetic and transcriptional profiles has been advanced by the application of genome-wide array-based profiling and large-scale sequencing efforts. Recent studies employing these techniques added in complementing the picture of the alterations and pathways most frequently involved in gliomagenesis and thus qualifying as promising targets for glioma diagnostics and therapy. Moreover, these approaches identified novel aberrations, for example, mutations in the isocitrate dehydrogenase 1 and 2 genes (IDH1, IDH2) and duplication/fusion of the BRAF oncogene, which are of diagnostic and prognostic importance in glioma patients. In addition, the discovery of genetic alterations that convey treatment resistence, such as MSH6 mutations, will contribute to enforce patient selection for more individualized therapies.

This brief review highlights selected large-scale molecular profiling studies published within the last year that significantly advanced our knowledge of the molecular biology of human gliomas and contributed novel glioma biomarkers of clinical interest.