Advances in the molecular genetics of gliomas — implications for classification and therapy

The 2016 WHO Classification of Tumours of the Central Nervous System reflects a paradigm shift, replacing traditional histology-based glioma diagnostics with an integrated histological and molecular classification system that enables more-precise tumour categorizationThe requisite diagnostic biomarkers in the 2016 WHO classification of gliomas are IDH1/2 (IDH) mutations, 1p/19q codeletion, H3F3A or HIST1H3B/C K27M (H3-K27M) mutations and C11orf95–RELA fusionsAdditional diagnostically relevant biomarkers include loss of nuclear ATRX expression, TERT-promoter mutations, KIAA1549–BRAF fusions, BRAF-V600E mutation, H3F3A-G34 mutation, and several other alterations associated with rare glioma entitiesMGMT-promoter methylation is predictive of benefit from alkylating chemotherapy in patients with IDH-wild-type glioblastoma; predictive biomarkers for targeted therapies, such as IDH1 and BRAF mutations, are also emergingNovel methods for large-scale DNA-methylation, copy-number and mutational profiling will further advance the assessment of glioma-associated molecular biomarkersClinical trials require assessment of molecular biomarkers as criteria for study entry and/or patient stratification; predictive DNA sequencing followed by targeted therapy will support the implementation of precision medicine in neuro-oncology