High-Grade Glioma, NOS (HGGNOS)

Overview

High-grade glioma, NOS (HGGNOS) encompasses WHO grade III and IV glial tumors that cannot be further classified into a specific defined entity by current molecular criteria. In pediatric patients, high-grade gliomas include diffuse intrinsic pontine glioma (DIPG)/DIFG, pediatric glioblastoma, and other high-grade infiltrating gliomas, frequently harboring H3K27M or H3G34R/V mutations (H3-3A/H3C2), ATRX loss, and PDGFRA amplification. Prognosis is poor.

Cohorts in the corpus

  • mixed_pipseq_2017 — PIPseq pediatric pan-cancer cohort (Columbia University Medical Center), which includes high-grade glioma NOS cases among 101 high-risk pediatric patients PMID:28007021.

Recurrent alterations

  • PIPseq cohort: HGGNOS cases included pediatric high-grade gliomas; H3-3A (H3F3A) K27M identified as HDAC-inhibitor target; CDK2 gain at 12q14.1 identified in one glioblastoma multiforme patient as a CDK4/6-inhibitor target; H3-3A K27M paired with FGFR1 N577K in one glioma patient PMID:28007021.

Subtypes

  • Diffuse intrinsic pontine glioma / diffuse midline glioma H3 K27-altered (DIFG).
  • Pediatric-type diffuse high-grade glioma, H3-wildtype.
  • Adult-type glioblastoma (IDH-wildtype, TERT promoter/EGFR amplification/+7/-10 signature).

Therapeutic landscape

  • Radiation therapy is standard; temozolomide is used for adult-type tumors with MGMT promoter methylation.
  • H3K27M mutant: panobinostat (HDAC inhibitor) under investigation.
  • FGFR-altered: FGFR inhibitors under investigation.

Sources

  • PMID:28007021 — Oberg et al. PIPseq pediatric pan-cancer sequencing program (n=101).

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