H3-3A

Overview

H3-3A encodes the replication-independent histone variant H3.3. Recurrent missense mutations at K27M (p.K28M in the mature protein) define diffuse midline glioma, H3 K27M-mutant, a WHO-recognized CNS tumor entity with poor prognosis.

Alterations observed in the corpus

  • H3-3A p.K28M (H3 K27M) was detected in CSF ctDNA, supporting the diagnosis of diffuse midline glioma in the csf_msk_2024 cohort (1,007 CSF samples, 711 patients) profiled by MSK-IMPACT PMID:39289779.
  • K27M mutation co-occurs with FGFR1 activation and NF1 alteration in pilocytic astrocytoma/glioblastoma; same K27M found in 3/48 pediatric GB samples in a screening cohort, often with FGFR1 mutation and NF1 loss PMID:23817572
  • H3-3A (histone H3.3) mutations were absent in the TCGA 2013 primary GBM cohort (n=291 WES), consistent with their previously reported occurrence in pediatric rather than adult GBM PMID:24120142
  • Only 2 samples mutated in a WGS pan-glioma dataset (n=1122), despite frequent involvement in pediatric gliomas; H3-3A (H3F3A) mutant status largely absent in adult diffuse glioma, supporting a distinct ALT mechanism (DAXX/H3.3-independent) in this population PMID:26824661
  • H3-3A (H3F3A) K28M (K27M) mutation identified in glioma and glioblastoma multiforme as an HDAC-inhibitor target; also co-occurred with FGFR1 N577K in one pediatric glioma patient PMID:28007021.

Cancer types (linked)

  • DIFG — H3-3A K27M mutation is the defining molecular alteration of diffuse midline glioma; detected in CSF ctDNA as a non-invasive diagnostic tool PMID:39289779.

Co-occurrence and mutual exclusivity

  • Not reported in the corpus.

Therapeutic relevance

  • H3 K27M mutation identifies patients eligible for emerging epigenetic-targeted therapies; CSF ctDNA detection provides a non-invasive route to molecular diagnosis in surgically inaccessible midline tumors PMID:39289779.

Open questions

  • None flagged in the corpus.

Sources

This page was processed by crosslinker on 2026-05-09. - PMID:23817572

This page was processed by crosslinker on 2026-05-09. - PMID:24120142

This page was processed by crosslinker on 2026-05-09. - PMID:26824661

This page was processed by entity-page-writer on 2026-05-15. - PMID:28007021

This page was processed by entity-page-writer on 2026-05-15.