Table 1 Molecular markers for the diagnosis and management of gliomas
From: EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood
Molecular marker | Biological function of affected genes | Diagnostic roles |
|---|---|---|
IDH1 R132 or IDH2 R172 mutation | Gain-of-function mutation | Distinguishes diffuse gliomas with IDH mutation from IDH-wild-type glioblastomas and other IDH-wild-type gliomas |
1p/19q codeletion | Inactivation of putative tumour suppressor genes on 1p (such as FUBP1) and 19q (such as CIC) | Distinguishes oligodendroglioma, IDH-mutant and 1p/19q-codeleted from astrocytoma, IDH-mutant |
Loss of nuclear ATRX | Cell proliferation and promotion of cellular longevity by alternative lengthening of telomeres | Loss of nuclear ATRX in an IDH-mutant glioma is diagnostic for astrocytic lineage tumours |
Histone H3 K27M mutation | Histone H3.3 (H3F3A) or histone H3.1 (HIST1H3B/C) missense mutation affecting epigenetic regulation of gene expression | Defining molecular feature of diffuse midline glioma, H3 K27M-mutant |
Histone H3.3 G34R/V mutation | Histone mutation affecting epigenetic regulation of gene expression | Defining molecular feature of diffuse hemispheric glioma, H3.3 G34-mutant |
MGMT promoter methylation | DNA repair | None, but is a predictive biomarker of benefit from alkylating chemotherapy in patients with IDH-wild-type glioblastoma |
Homozygous deletion of CDKN2A/CDKN2B | Encode cyclin-dependent kinase inhibitors 2A and 2B and tumour suppressor ARF, which function as regulators of Rb1 and p53-dependent signalling | A marker of poor outcome and WHO grade 4 disease in IDH-mutant astrocytomas |
EGFR amplification | Cell proliferation, invasion and resistance to induction of apoptosis | EGFR amplification occurs in ~40–50% of glioblastoma, IDH wild type Molecular marker of glioblastoma,IDH wild type, WHO grade 4 (ref.3) |
TERT promotor mutation | Cell proliferation; promotes cellular longevity by increasing TERT expression | TERT promoter mutation occurs in ~70% of glioblastoma, IDH wild type and >95% of oligodendroglioma, IDH-mutant and 1p/19q-codeleted Molecular marker of glioblastoma, IDH wild type, WHO grade 4 (ref.3) |
+7/–10 cytogenetic signature | Gain of chromosome 7 (harbouring genes encoding, among others, PDGFA and EGFR) combined with loss of chromosome 10 (harbouring genes including PTEN and MGMT) | Molecular marker of glioblastoma, IDH wild type, WHO grade 4 (ref.3) |
BRAFV600E mutation | Oncogenic driver mutation leading to MAPK pathway activation | Rare in adult diffuse gliomas but amenable to pharmacological intervention |
