ArticlePLoS genetics2021
The H3.3K27M oncohistone affects replication stress outcome and provokes genomic instability in pediatric glioma.
Article in PLoS genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Contribution of histone variants to aneuploidy: a cancer perspective.Frontiers in genetics · 2023Pooled it
- The future of targeted therapies for pediatric central nervous system tumors.Neuro-oncology advances · 2026Review
- Article
- Role of epigenetics in paediatric cancer pathogenesis & drug resistance.British journal of cancer · 2025Review
- H3.1K27M-induced misregulation of the TONSOKU-H3.1 pathway causes genomic instability.Nature communications · 2025Article
- The histone H3.3 K27M mutation suppresses Ser31phosphorylation and mitotic fidelity, which can directly drive gliomagenesis.Current biology : CB · 2025Article
- Extracellular Histones Profiles of Pediatric H3K27-Altered Diffuse Midline Glioma.Molecular diagnosis & therapy · 2025Article
- Multi-omics approaches reveal that diffuse midline gliomas present altered DNA replication and are susceptible to replication stress therapy.Genome biology · 2024Article
- Histone H3 mutations and their impact on genome stability maintenance.Biochemical Society transactions · 2024Review
- KIFC3 promotes the proliferation, migration and invasion of non-small cell lung cancer through the PI3K/AKT signaling pathway.Scientific reports · 2024Article
- Review
- Epigenomic insights into common human disease pathology.Cellular and molecular life sciences : CMLS · 2024Review
- Aberrant DNA repair reveals a vulnerability in histone H3.3-mutant brain tumors.Nucleic acids research · 2024Article
- Methylation of histone H3 lysine 36 is a barrier for therapeutic interventions of head and neck squamous cell carcinoma.Genes & development · 2024Article
- Emerging roles of cancer-associated histone mutations in genomic instabilities.Frontiers in cell and developmental biology · 2024Review
- Methylation of histone H3 lysine 36 is a barrier for therapeutic interventions of head and neck squamous cell carcinoma.bioRxiv : the preprint server for biology · 2023Article
- The cell-cycle choreography of H3 variants shapes the genome.Molecular cell · 2023Review
- Knockout tales: the versatile roles of histone H3.3 in development and disease.Epigenetics & chromatin · 2023Review
- The Regulation of m6A Modification in Glioblastoma: Functional Mechanisms and Therapeutic Approaches.Cancers · 2023Review
- Oncohistones and disrupted development in pediatric-type diffuse high-grade glioma.Cancer metastasis reviews · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
While comprehensive molecular profiling of histone H3.3 mutant pediatric high-grade glioma has revealed extensive dysregulation of the chromatin landscape, the exact mechanisms driving tumor formation remain poorly understood. Since H3.3 mutant gliomas also exhibit high levels of copy number alterations, we set out to address if the H3.3K27M oncohistone leads to destabilization of the genome. Hereto, we established a cell culture model allowing inducible H3.3K27M expression and observed an increase in mitotic abnormalities. We also found enhanced interaction of DNA replication factors with H3.3K27M during mitosis, indicating replication defects. Further functional analyses revealed increased genomic instability upon replication stress, as represented by mitotic bulky and ultrafine DNA bridges. This co-occurred with suboptimal 53BP1 nuclear body formation after mitosis in vitro, and in human glioma. Finally, we observed a decrease in ultrafine DNA bridges following deletion of the K27M mutant H3F3A allele in primary high-grade glioma cells. Together, our data uncover a role for H3.3 in DNA replication under stress conditions that is altered by the K27M mutation, promoting genomic instability and potentially glioma development.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.