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TERT promoter mutations are central to WHO CNS tumor classification (2021 5th edition): (...

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

IDBMA-TERT-GLIOMA
TypeActionability
Statusreviewed 2026-05-04 | pending_clinical_signoff | actionability review required
DiseasesDIS-GBM
SourcesSRC-EANO-GBM-2024 SRC-NCCN-CNS-2025

Actionability Facts

BiomarkerBIO-TERT
VariantTERT promoter mutation (C228T or C250T) — WHO CNS tumor classification context: GBM (IDH-wild-type; required for molecular diagnosis), oligodendroglioma (IDH-mutant + 1p/19q co-deletion + TERT = canonical)
DiseaseDIS-GBM
ESCAT tierIIB
Recommended combinationsStupp protocol: RT 60 Gy/30 fr + temozolomide 75 mg/m² PO QD during RT, then temozolomide 150–200 mg/m² PO days 1–5 q28d × 6 cycles (MGMT-guided; not TERT-guided), Tumor treating fields (TTF; Optune) — FDA-approved for GBM maintenance (EF-14 trial); not TERT-specific
Evidence summaryTERT promoter mutations are central to WHO CNS tumor classification (2021 5th edition): (1) GBM (IDH-wildtype, WHO grade 4): TERT promoter mutation is one of three molecular defining features (together with EGFR amplification and chromosome +7/-10 copy number changes). An IDH-wildtype diffuse astrocytoma with any of these features meets criteria for molecular GBM diagnosis regardless of histologic grade. TERT alone: ~70–80% of GBM. TERT mutation identifies the most aggressive tumor biology within IDH-wildtype astrocytomas. No TERT-directed therapy available. (2) Oligodendroglioma (IDH-mutant, 1p/19q co-deleted): TERT promoter mutation is present in ~70% and is part of the canonical molecular definition. TERT testing is used to confirm oligodendroglioma classification (IDH + 1p/19q + TERT triple positive). (3) IDH-mutant astrocytoma (grade 2–4): TERT promoter mutation is less common (~20%) and associated with worse prognosis within IDH-mutant tumors; CDKN2A/B homozygous deletion is the main grade 4 determinant in IDH-mutant astrocytoma. Standard treatment for GBM is unchanged by TERT...

Notes

ESCAT IIB: TERT mutation in glioma is a diagnostic classifier and prognostic marker, not a therapeutic target. TERT testing is part of the mandatory integrated molecular workup for all diffuse gliomas per WHO CNS 5th edition (2021): IDH1/2, ATRX, 1p/19q, CDKN2A/B, TERT promoter, MGMT promoter (treatment-predictive). Note: TERT promoter is NOT covered by most routine exome sequencing panels — dedicated panel or separate Sanger/ddPCR assay needed. Oligodendroglioma precision: triple positive (IDH+/1p19q-codel+/TERT+) is the most reliable molecular classifier; TERT-negative IDH+/1p19q-codel tumors are diagnostically ambiguous. Treatment for TERT-positive GBM is identical to TERT-negative GBM: RT + temozolomide ± bevacizumab; no clinical benefit from TERT-specific approaches has been demonstrated.

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