ArticleCancer discovery2022
Epigenome Programming by H3.3K27M Mutation Creates a Dependence of Pediatric Glioma on SMARCA4.
Article in Cancer discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 46 citations in OpenAlex.
- The roles of chromatin remodeling and 3D genome organization in cancers: from mechanistic insights to emerging treatment options.Molecular cancer · 2026Review
- Emerging structural insights into PRC2 function in development and disease.Trends in biochemical sciences · 2026Review
- Macrophage-associated SLAMF9 is a potential therapeutic target for glioma.Translational cancer research · 2026Article
- H3K27-altered diffuse midline glioma of the adult thoracic spinal cord: A case report with literature review and clinical insights.Surgical neurology international · 2026Article
- Decoding Gene Expression Changes in Cerebral Tumors: Before and After Radiotherapy.Medicinal research reviews · 2025Review
- Loss of SMARCB1 evokes targetable epigenetic vulnerabilities in epithelioid sarcoma.Cancer communications (London, England) · 2025Article
- An oncohistone-driven H3.3K27M/CREB5/ID1 axis maintains the stemness and malignancy of diffuse intrinsic pontine glioma.Nature communications · 2025Article
- Targeted delivery of napabucasin with radiotherapy improves outcomes in diffuse midline glioma.Neuro-oncology · 2025Article
- Synthetic lethal strategies for the development of cancer therapeutics.Nature reviews. Clinical oncology · 2025Review
- Epigenetic reprogramming in pediatric gliomas: from molecular mechanisms to therapeutic implications.Trends in cancer · 2024Review
- CHD2 Regulates Neuron-Glioma Interactions in Pediatric Glioma.Cancer discovery · 2024Article
- Chromatin remodellers as therapeutic targets.Nature reviews. Drug discovery · 2024Review
- Developmental origins shape the paediatric cancer genome.Nature reviews. Cancer · 2024Review
- H3Journal of clinical medicine · 2024Review
- Targeting SWI/SNF Complexes in Cancer: Pharmacological Approaches and Implications.Epigenomes · 2024Review
- Does H3K27M Mutation Impact Survival Outcome of High-Grade Spinal Cord Astrocytoma?Neurospine · 2023Article
- Decoding key cell sub-populations and molecular alterations in glioblastoma at recurrence by single-cell analysis.Acta neuropathologica communications · 2023Article
- Genomic profiling and prognostic factors of H3 K27M-mutant spinal cord diffuse glioma.Brain pathology (Zurich, Switzerland) · 2023Article
- Oncohistones and disrupted development in pediatric-type diffuse high-grade glioma.Cancer metastasis reviews · 2023Review
- Targeting SWI/SNF ATPases in H3.3K27M diffuse intrinsic pontine gliomas.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
Corrections and comments
- Commented on by
- Commented on by
- Commented on by
- Comment on
Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
Patients with diffuse midline gliomas that are H3K27 altered (DMG) display a dismal prognosis. However, the molecular mechanisms underlying DMG tumorigenesis remain poorly defined. Here we show that SMARCA4, the catalytic subunit of the mammalian SWI/SNF chromatin remodeling complex, is essential for the proliferation, migration, and invasion of DMG cells and tumor growth in patient-derived DMG xenograft models. SMARCA4 colocalizes with SOX10 at gene regulatory elements to control the expression of genes involved in cell growth and the extracellular matrix (ECM). Moreover, SMARCA4 chromatin binding is reduced upon depletion of SOX10 or H3.3K27M, a mutation occurring in about 60% DMG tumors. Furthermore, the SMARCA4 occupancy at enhancers marked by both SOX10 and H3K27 acetylation is reduced the most upon depleting the H3.3K27M mutation. Taken together, our results support a model in which epigenome reprogramming by H3.3K27M creates a dependence on SMARCA4-mediated chromatin remodeling to drive gene expression and the pathogenesis of H3.3K27M DMG. SIGNIFICANCE: DMG is a deadly pediatric glioma currently without effective treatments. We discovered that the chromatin remodeler SMARCA4 is essential for the proliferation of DMG with H3K27M mutation in vitro and in vivo, identifying a potentially novel therapeutic approach to this disease. See related commentary by Beytagh and Weiss, p. 2730. See related article by Panditharatna et al., p. 2880. This article is highlighted in the In This Issue feature, p. 2711.
Indexed as
Identifiers
What OpenQuestion holds
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.