ArticleCancer discovery2013
Histone H3.3. mutations drive pediatric glioblastoma through upregulation of MYCN.
Article in Cancer discovery, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 181 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
181 citing papers in PubMed, 2 syntheses or guidelines pooled it, 313 citations in OpenAlex.
- Extent of Tumor Resection and Survival in Pediatric Patients With High-Grade Gliomas: A Systematic Review and Meta-analysis.JAMA network open · 2022Pooled it
- Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma.Cancer cell · 2017Pooled it
- Molecular, Pathological, Radiological, and Immune Profiling of Non-brainstem Pediatric High-Grade Glioma from the HERBY Phase II Randomized Trial.Cancer cell · 2018Trial
- Review
- Evidence for coordinate CTCF and histone H3.3 activities in K27M diffuse midline gliomas.Acta neuropathologica communications · 2026Article
- Therapeutic efficacy of dendritic cell vaccination in a novel syngeneic mouse model of diffuse hemispheric glioma, H3 G34-mutant.Journal of neuro-oncology · 2026Article
- "Targeting NF-κB epigenetic activation and DNA repair deficiency in G34-mutant pediatric diffuse hemispheric glioma with nanoparticles combining PARP inhibition and immune stimulation mediated by CpG dinucleotides".bioRxiv : the preprint server for biology · 2026Article
- Implications of canonical histone H3.1 and histone variant H3.3 in cancer.Open biology · 2025Review
- A review of diffuse hemispheric glioma, H3 G34-mutant disease development, DNA repair, microenvironment, and treatments on the horizon.NPJ precision oncology · 2025Review
- Role of epigenetics in paediatric cancer pathogenesis & drug resistance.British journal of cancer · 2025Review
- An oncohistone-driven H3.3K27M/CREB5/ID1 axis maintains the stemness and malignancy of diffuse intrinsic pontine glioma.Nature communications · 2025Article
- Targeting the MYCN-MDM2 pathways for cancer therapy: Are they druggable?Genes & diseases · 2025Review
- H3.3-G34R Mutation-Mediated Epigenetic Reprogramming Leads to Enhanced Efficacy of Immune Stimulatory Gene Therapy in Diffuse Hemispheric Gliomas.bioRxiv : the preprint server for biology · 2025Article
- MYCN as an oncogene in pediatric brain tumors.Frontiers in oncology · 2025Review
- A high-throughput screening platform to identifyFrontiers in oncology · 2025Article
- (B)On(e)-cohistones and the epigenetic alterations at the root of bone cancer.Cell death and differentiation · 2025Review
- GABAergic neuronal lineage development determines clinically actionable targets in diffuse hemispheric glioma, H3G34-mutant.Cancer cell · 2024Article
- Review
- Molecular and Pathological Features of Paediatric High-Grade Gliomas.International journal of molecular sciences · 2024Review
- Epigenetics to clinicopathological features: a bibliometric analysis of H3 G34-mutant diffuse hemispheric glioma literature.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2024Review
121 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 2 countries.
Funding
Abstract
unlabelledChildren and young adults with glioblastoma (GBM) have a median survival rate of only 12 to 15 months, and these GBMs are clinically and biologically distinct from histologically similar cancers in older adults. They are defined by highly specific mutations in the gene encoding the histone H3.3 variant H3F3A , occurring either at or close to key residues marked by methylation for regulation of transcription—K27 and G34. Here, we show that the cerebral hemisphere-specific G34 mutation drives a distinct expression signature through differential genomic binding of the K36 trimethylation mark (H3K36me3). The transcriptional program induced recapitulates that of the developing forebrain, and involves numerous markers of stem-cell maintenance, cell-fate decisions, and self-renewal.Critically, H3F3A G34 mutations cause profound upregulation of MYCN , a potent oncogene that is causative of GBMs when expressed in the correct developmental context. This driving aberration is selectively targetable in this patient population through inhibiting kinases responsible for stabilization of the protein. SIGNIFICANCE: We provide the mechanistic explanation for how the fi rst histone gene mutation inhuman disease biology acts to deliver MYCN, a potent tumorigenic initiator, into a stem-cell compartment of the developing forebrain, selectively giving rise to incurable cerebral hemispheric GBM. Using synthetic lethal approaches to these mutant tumor cells provides a rational way to develop novel and highly selective treatment strategies
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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.