# Histone H3F3A and HIST1H3B K27M mutations define two subgroups of diffuse intrinsic pontine gliomas with different prognosis and phenotypes

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## TL;DR

Paper by Jacques Grill indexed on Europe PMC as PubMed record 26399631, in Acta neuropathologica (2015), one of the most cited records naming an author with this name at Gustave Roussy.

## Summary

Diffuse intrinsic pontine glioma (DIPG) is the most severe paediatric solid tumour, with no significant therapeutic progress made in the past 50 years. Recent studies suggest that diffuse midline glioma, H3-K27M mutant, may comprise more than one biological entity. The aim of the study was to determine the clinical and biological variables that most impact their prognosis. Ninety-one patients with classically defined DIPG underwent a systematic stereotactic biopsy and were included in this observational retrospective study. Histone H3 genes mutations were assessed by immunochemistry and direct sequencing, whilst global gene expression profiling and chromosomal imbalances were determined by microarrays. A full description of the MRI findings at diagnosis and at relapse was integrated with the molecular profiling data and clinical outcome. All DIPG but one were found to harbour either a somatic H3-K27M mutation and/or loss of H3K27 trimethylation. We also discovered a novel K27M mutation in HIST2H3C, and a lysine-to-isoleucine substitution (K27I) in H3F3A, also creating a loss of trimethylation. Patients with tumours harbouring a K27M mutation in H3.3 (H3F3A) did not respond clinically to radiotherapy as well, relapsed significantly earlier and exhibited more metastatic recurrences than those in H3.1 (HIST1H3B/C). H3.3-K27M-mutated DIPG have a proneural/oligodendroglial phenotype and a pro-metastatic gene expression signature with PDGFRA activation, while H3.1-K27M-mutated tumours exhibit a mesenchymal/astrocytic phenotype and a pro-angiogenic/hypoxic signature supported by expression profiling and radiological findings. H3K27 alterations appear as the founding event in DIPG and the mutations in the two main histone H3 variants drive two distinct oncogenic programmes with potential specific therapeutic targets.

Indexed on Europe PMC as PubMed record 26399631 (DOI 10.1007/s00401-015-1478-0). Its author list gives "Grill J" with the affiliation "UMR8203 "Vectorologie et Thérapeutiques Anticancéreuses", CNRS, Gustave Roussy, Univ. Paris-Sud, Université Paris-Saclay, 94805, Villejuif, France. jacques.grill@gustaveroussy.fr", which names Gustave Roussy; that is how the record was matched to Jacques Grill, and no figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: Acta neuropathologica
- Year: 2015
- DOI: 10.1007/s00401-015-1478-0
- Authors: Castel D, Philippe C, Calmon R, et al.
- What it means: One of the most cited papers Europe PMC returns for Jacques Grill at Gustave Roussy, so it is a natural starting point for reading their work. The record was linked automatically from the author list and affiliation; read the abstract above and the paper itself before relying on any figure.
- Caveats: Matched to the person by surname, initials and an affiliation string naming the institution on the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.; Two authors sharing a surname, initials and institution cannot be told apart by this method; the person's profile links are the place to confirm authorship.

## Sources

- Acta Neuropathol 2015: https://doi.org/10.1007/s00401-015-1478-0
- PubMed: https://pubmed.ncbi.nlm.nih.gov/26399631/
- Europe PMC: https://europepmc.org/article/MED/26399631

## Connected records

- people: [Jacques Grill](https://onco.cc/people/jacques-grill/)

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