Oligodendroglioma, IDH-mutant, and 1p/19q-Codeleted, Grade 3 (ODG3)

Overview

ODG3 (historically called anaplastic oligodendroglioma, WHO grade 3) is a diffuse glioma defined by IDH1 or IDH2 mutation together with 1p/19q codeletion. Under the 2021 WHO Classification, this combination is required for diagnosis; the grade 3 designation indicates mitotic activity or microvascular proliferation without necrosis. Parent OncoTree code: ODG. It is associated with a relatively favorable prognosis compared to IDH-mutant astrocytomas of equivalent grade, particularly in the 1p/19q-codeleted subset.

Cohorts in the corpus

  • odg_msk_2017 — 41-patient multicenter phase II trial cohort (NCT00588523); 19 tumors subjected to NGS with MSK-IMPACT 410-gene panel.

Recurrent alterations

  • TERT promoter mutations in 18/19 (95%) sequenced tumors — the most frequent alteration in ODG3, characteristic of the 1p/19q-codeleted lineage. PMID:28472509
  • IDH1 R132H in 13/19 (68%); IDH2 R172K in 1/19; defining mutations absent in 1p/19q-intact glioblastoma-like cases. PMID:28472509
  • CIC mutations in 10/19 (53%); FUBP1 in 5/19 (26%) — canonical 19q and 1p drivers respectively. PMID:28472509
  • NOTCH1 mutated in 6/19 (32%); NOTCH2 in 5/19 (26%). PMID:28472509
  • CDK4 amplification in 2/19 (10.5%; OncoKB Level 2B); PIK3CA mutations (E365K, H1047R) in 2/19 (10.5%; OncoKB Level 3B). PMID:28472509
  • 1p/19q-intact tumors (glioblastoma-like): EGFR amplification/mutation, NF1 mutation, MDM2 amplification, IDH1/2 wild-type — these represent diagnostic misclassification; NGS-confirmed 1p/19q status recommended over FISH alone. PMID:28472509
  • In a phase II multicenter trial (NCT00588523, n=41), induction temozolomide followed by high-dose thiotepa/busulfan plus autologous stem-cell transplant achieved 2-year PFS of 86% and 5-year OS of 100% in transplanted anaplastic oligodendroglioma patients (85% 1p/19q codeleted); NGS (MSK-IMPACT 410-gene panel) in 19 tumors confirmed TERT promoter (95%), IDH1 R132H (68%), CIC (53%), NOTCH1 (32%), FUBP1 (26%) as the dominant alteration landscape. PMID:28472509

Subtypes

  • 1p/19q-codeleted (true ODG3): IDH-mutant, TERT-promoter-mutant, CIC/FUBP1-mutant; favorable prognosis; chemotherapy-alone strategies viable.
  • 1p/19q-intact (glioblastoma-like): IDH wild-type, EGFR/NF1/MDM2-driven; progresses early; chemotherapy alone is not appropriate.

Therapeutic landscape

  • Induction temozolomide (6 cycles, 200 mg/m²) followed by myeloablative thiotepa/busulfan with autologous stem-cell transplant deferred radiotherapy in 52% of 1p/19q-codeleted patients at 5 years (5-year OS 93.4%); TMZ was non-inferior to prior PCV-induction regimens in cross-trial comparison (HR 3.38 for OS, P=0.005). PMID:28472509
  • IDH1/IDH2 inhibitors (OncoKB Level 3B for IDH1 R132H / IDH2 R172K) represent a potential targeted approach. PMID:28472509

Sources

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