Table 1.
Recommended biomarkers for testing and their clinical implications in AYA glioma.
| Genes/Molecular profiles characteristically altered | Clinically relevant biomarkers (diagnostic, predictive or prognostic) | |
|---|---|---|
| Adult-type diffuse gliomas | ||
| Astrocytoma, IDH-mutant (CNS WHO grade 2, 3, 4) |
IDH1, IDH2, ATRX, TP53, CDKN2A/B | ATRX nuclear loss is diagnostic for astrocytic- lineage tumors in an IDH-mutant glioma TP53 mutations are commonly found in astrocytomas CDKN2A/B homozygous deletion is a marker of poor prognosis and upgrades Grade 2/3 IDH-mutant astrocytomas to Grade 4 astrocytomas |
| Oligodendroglioma, IDH-mutant, and 1p/19q-codeleted (CNS WHO grades 2, 3) |
IDH1, IDH2, 1p/19q, TERT promoter, CIC, FUBP1, NOTCH1 | 1p/19q codeletion distinguishes oligodendroglioma from astrocytoma, within IDH-mutant glioma |
| Glioblastoma, IDH-wildtype (CNS WHO grade 4) |
IDH-wildtype, TERT promoter, chromosomes 7+/10-, EGFR |
IDH-wildtype, and one of: TERT promoter mutation; chromosome 7+/10-; or EGFR amplification, defines molecular GBM irrespective of histologic grade MGMT promoter methylation is a prognostic biomarker independent of treatment with alkylating chemotherapy and a predictive biomarker of benefit from alkylating chemotherapy in patients with IDH-wildtype glioblastoma |
| Pediatric-type diffuse gliomas | ||
| Low-grade glioma (IDH-wildtype) | BRAF, FGFR1, FGFR2, MYBL1, MYB, or other MAPK alterations, CDKN2A |
In pediatric LGG, homozygous deletion in CDKN2A carry a worse prognosis. RAF/RAS/MAPK alterations can offer targeted therapy options |
| High-grade glioma (hemispheric) High-grade glioma (midline) |
H3 G34R H3 K27M |
In pediatric HGG, H3 G34R and H3 K27M alterations are diagnostic and confer a poor prognosis |
| High-grade glioma (IDH-wildtype and H3-wildtype) | BRAF V600E*, FGFR1*, MYBL*, MYB*, MYCN, PDGFRA, EGFR, p53, or other MAPK alterations, MLH1, MSH2, MSH6 and PMS | *Mutations in BRAF V600E, FGFR1, MYBL, MYB carry a better prognosis and are more common in low-grade glioma RAF/RAS/MAPK alterations can offer targeted therapy options |
| Glioneuronal tumors | ||
| Dysembryoplastic neuroepithelial tumor, Ganglioglioma, Multinodular and vacuolating neuronal tumor, and others | FGFR1 in DNETs, MAPK alterations in MVNTs |
RAF/RAS/MAPK alterations can offer targeted therapy options |