ArticleActa neuropathologica2019
H3.3 K27M depletion increases differentiation and extends latency of diffuse intrinsic pontine glioma growth in vivo.
Article in Acta neuropathologica, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 77 papers.
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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.
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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
77 citing papers in PubMed, 122 citations in OpenAlex.
- Exon-skipping antisense oligonucleotides for H3.3K27M-altered diffuse midline glioma therapy.Molecular therapy. Nucleic acids · 2026Article
- CXorf67 in malignancies: Deciphering epigenetic landscapes and clinical implications for precision oncology.Genes & diseases · 2026Review
- Cell autonomous regional differences in oligodendrocyte lineage development and responses to oncohistone H3.3 K27M.Nature communications · 2026Article
- H3K27me3 spreading organizes canonical PRC1 chromatin architecture to regulate developmental programs.Nature genetics · 2026Article
- Evidence for coordinate CTCF and histone H3.3 activities in K27M diffuse midline gliomas.Acta neuropathologica communications · 2026Article
- Deciphering the tumor microenvironment and role of immunotherapy in diffuse midline glioma: A scoping review.Neuro-oncology · 2026Article
- Developmental reprogramming underlies chemotherapy resistance in favorable-histology Wilms tumor.Cell reports · 2026Article
- Lactylation fuels nucleotide biosynthesis and facilitates deuterium metabolic imaging of tumor proliferation in preclinical models of H3K27M-mutant gliomas.Science translational medicine · 2026Article
- A bibliometric analysis of progress and trends in pediatric glioma research.Discover oncology · 2026Article
- SUV39H1 regulates progression of pediatric diffuse high-grade gliomas through modulation of β-catenin/TCF4 levels.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Ezh2 Loss-of-Function Alters Zebrafish Cerebellum Development.International journal of molecular sciences · 2025Article
- The Bermuda Triangle of paediatric brain cancers: epigenetics, developmental timing window and cell of origin.Cancer metastasis reviews · 2025Review
- Review
- Identification of urinary metabolic biomarkers for histone 3 lysine27-to-methionine mutation diagnosis in brainstem gliomas.Neuro-oncology · 2025Article
- Establishment of xenografts and methods to evaluate tumor burden for the three most frequent subclasses of pediatric-type diffuse high grade gliomas.Journal of neuro-oncology · 2025Article
- Histone H3E50K remodels chromatin to confer oncogenic activity and support an EMT phenotype.NAR cancer · 2025Article
- Aberrant histone modifications in pediatric brain tumors.Frontiers in oncology · 2025Review
- An E2 ubiquitin-conjugating enzyme links diubiquitinated H2B to H3K27M oncohistone function.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The Landscape of Pediatric High-Grade Gliomas: The Virtues and Pitfalls of Pre-Clinical Models.Biology · 2024Review
- Pediatric Diffuse Midline Glioma H3K27-Altered: From Developmental Origins to Therapeutic Challenges.Cancers · 2024Review
17 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
26 authors at 3 institutions in 1 country.
Funding
Abstract
Histone H3 K27M mutation is the defining molecular feature of the devastating pediatric brain tumor, diffuse intrinsic pontine glioma (DIPG). The prevalence of histone H3 K27M mutations indicates a critical role in DIPGs, but the contribution of the mutation to disease pathogenesis remains unclear. We show that knockdown of this mutation in DIPG xenografts restores K27M-dependent loss of H3K27me3 and delays tumor growth. Comparisons of matched DIPG xenografts with and without K27M knockdown allowed identification of mutation-specific effects on the transcriptome and epigenome. The resulting transcriptional changes recapitulate expression signatures from K27M primary DIPG tumors and are strongly enriched for genes associated with nervous system development. Integrated analysis of ChIP-seq and expression data showed that genes upregulated by the mutation are overrepresented in apparently bivalent promoters. Many of these targets are associated with more immature differentiation states. Expression profiles indicate K27M knockdown decreases proliferation and increases differentiation within lineages represented in DIPG. These data suggest that K27M-mediated loss of H3K27me3 directly regulates a subset of genes by releasing poised promoters, and contributes to tumor phenotype and growth by limiting differentiation. The delayed tumor growth associated with knockdown of H3 K27M provides evidence that this highly recurrent mutation is a relevant therapeutic target.
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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.