Diagnostic, prognostic and predictive relevance of molecular markers in gliomas

Neuropathol Appl Neurobiol. 2015 Oct;41(6):694-720. doi: 10.1111/nan.12246. Epub 2015 Jun 10.


The advances of genome-wide 'discovery platforms' and the increasing affordability of the analysis of significant sample sizes have led to the identification of novel mutations in brain tumours that became diagnostically and prognostically relevant. The development of mutation-specific antibodies has facilitated the introduction of these convenient biomarkers into most neuropathology laboratories and has changed our approach to brain tumour diagnostics. However, tissue diagnosis will remain an essential first step for the correct stratification for subsequent molecular tests, and the combined interpretation of the molecular and tissue diagnosis ideally remains with the neuropathologist. This overview will help our understanding of the pathobiology of common intrinsic brain tumours in adults and help guiding which molecular tests can supplement and refine the tissue diagnosis of the most common adult intrinsic brain tumours. This article will discuss the relevance of 1p/19q codeletions, IDH1/2 mutations, BRAF V600E and BRAF fusion mutations, more recently discovered mutations in ATRX, H3F3A, TERT, CIC and FUBP1, for diagnosis, prognostication and predictive testing. In a tumour-specific topic, the role of mitogen-activated protein kinase pathway mutations in the pathogenesis of pilocytic astrocytomas will be covered.

Keywords: 1p/19q codeletion; ATRX; IDH mutation; biomarker; glioblastoma; oligodendroglioma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Astrocytoma / diagnosis*
  • Astrocytoma / genetics*
  • Biomarkers, Tumor / genetics*
  • Brain Neoplasms / diagnosis*
  • Brain Neoplasms / epidemiology
  • Brain Neoplasms / genetics*
  • Chromosomes, Human, Pair 1
  • Chromosomes, Human, Pair 19
  • DNA Helicases / genetics
  • DNA Modification Methylases / genetics
  • DNA Repair Enzymes / genetics
  • DNA-Binding Proteins / genetics
  • Disease-Free Survival
  • Glioma / diagnosis*
  • Glioma / epidemiology
  • Glioma / genetics*
  • Histones / genetics
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • MAP Kinase Signaling System / genetics
  • Mutation
  • Nuclear Proteins / genetics
  • Prognosis
  • Proto-Oncogene Proteins B-raf / genetics
  • RNA-Binding Proteins
  • Repressor Proteins / genetics
  • Telomerase / genetics
  • Tumor Suppressor Proteins / genetics
  • X-linked Nuclear Protein


  • Biomarkers, Tumor
  • CIC protein, human
  • DNA-Binding Proteins
  • FUBP1 protein, human
  • Histones
  • Nuclear Proteins
  • RNA-Binding Proteins
  • Repressor Proteins
  • Tumor Suppressor Proteins
  • Isocitrate Dehydrogenase
  • isocitrate dehydrogenase 2, human
  • IDH1 protein, human
  • DNA Modification Methylases
  • MGMT protein, human
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • TERT protein, human
  • Telomerase
  • DNA Helicases
  • ATRX protein, human
  • X-linked Nuclear Protein
  • DNA Repair Enzymes