ArticleScience translational medicine2021
Epigenetically defined therapeutic targeting in H3.3G34R/V high-grade gliomas.
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Article in Science translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30citing papers in PubMed
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30 citing papers in PubMed.
- Review
- Potent anti-tumor preclinical efficacy of B7-H3 CAR-T cells in H3G34-mutant, Diffuse Hemispheric Glioma.Neuro-oncology · 2026Article
- Single-cell multi-omic analyses resolve the cellular diversity of ALK/ROS1/MET/NTRK-fused gliomas in infants and older children.bioRxiv : the preprint server for biology · 2026Article
- Targeting SYK to alleviate MDSC-driven immunosuppression and augment anti-PD1 efficacy.Science China. Life sciences · 2026Article
- The JMJD family histone demethylases: structure, mechanism of action, diseases and therapeutic targets.Molecular biomedicine · 2026Review
- First-in-child phase I trial of p-STAT3 inhibitor WP1066 in pediatric brain tumor patients.JCI insight · 2026Article
- Illuminating radiogenomic signatures in pediatric-type diffuse gliomas: insights into molecular, clinical, and imaging correlations. Part I: high-grade group.La Radiologia medica · 2025Review
- The Bermuda Triangle of paediatric brain cancers: epigenetics, developmental timing window and cell of origin.Cancer metastasis reviews · 2025Review
- A review of diffuse hemispheric glioma, H3 G34-mutant disease development, DNA repair, microenvironment, and treatments on the horizon.NPJ precision oncology · 2025Review
- Current Landscape of Preclinical Models for Pediatric Gliomas: Clinical Implications and Future Directions.Cancers · 2025Review
- Role of epigenetics in paediatric cancer pathogenesis & drug resistance.British journal of cancer · 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
- Old players and new insights: unraveling the role of RNA-binding proteins in brain tumors.Theranostics · 2025Review
- Aberrant histone modifications in pediatric brain tumors.Frontiers in oncology · 2025Review
- Immuno-oncological interactions between meningeal lymphatics and glioblastoma: from mechanisms to therapies.Theranostics · 2025Review
- Review
- Glioma.Nature reviews. Disease primers · 2024Review
- Mutant KRAS Mediates circARFGEF2 Biogenesis to Promote Lymphatic Metastasis of Pancreatic Ductal Adenocarcinoma.Cancer research · 2023Article
- Review
- A Compendium of Syngeneic, Transplantable Pediatric High-Grade Glioma Models Reveals Subtype-Specific Therapeutic Vulnerabilities.Cancer discovery · 2023Article
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Authors and funding
30 authors.
Stefan R SwehaLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.ORCID 0000-0002-1807-6770
Chan ChungLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.ORCID 0000-0003-0510-8996
Siva Kumar NatarajanLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.ORCID 0000-0002-9663-079X
Pooja PanwalkarLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.ORCID 0000-0001-7223-0452
Matthew PunLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.ORCID 0000-0002-4766-4301
Amer GhaliLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.ORCID 0000-0001-9580-587X
Jill BaylissLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.ORCID 0000-0002-7995-5584
Drew PrattLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.ORCID 0000-0003-3583-8308
Anand ShankarDepartment of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Visweswaran RavikumarDepartment of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.ORCID 0000-0003-4670-3898
Arvind RaoDepartment of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.ORCID 0000-0002-9613-426X
Marcin CieslikDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Kari Wilder-RomansDepartment of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Andrew J ScottDepartment of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.ORCID 0000-0002-0835-4888
Daniel R WahlDepartment of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Selin JessaQuantitative Life Sciences, McGill University, Montreal, Quebec H3A 2A7, Canada.ORCID 0000-0003-4192-6523
Claudia L KleinmanLady Davis Research Institute, Jewish General Hospital, Montreal, Quebec H3T 1E2, Canada.
Nada JabadoDepartment of Human Genetics, McGill University, Montreal, Quebec H3A 0C7, Canada.ORCID 0000-0003-2485-3692
Alan MackayDivision of Molecular Pathology and Cancer Therapeutics, Institute of Cancer Research, London SM2 5NG, UK.ORCID 0000-0003-3323-4017
Chris JonesDivision of Molecular Pathology and Cancer Therapeutics, Institute of Cancer Research, London SM2 5NG, UK.ORCID 0000-0001-8118-2296
Daniel MartinezDepartment of Pathology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.ORCID 0000-0002-4723-9989
Mariarita SantiDepartment of Pathology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Alexander R JudkinsDepartment of Pathology, Children's Hospital of Los Angeles, Los Angeles, CA 90027, USA.ORCID 0000-0002-9242-3769
Viveka Nand YadavDepartment of Pediatrics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Tingting QinDepartment of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Timothy N PhoenixDivision of Pharmaceutical Sciences, College of Pharmacy, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.ORCID 0000-0003-4771-4003
Carl J KoschmannDepartment of Pediatrics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Suzanne J BakerDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.ORCID 0000-0002-5833-472X
Arul M ChinnaiyanDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.ORCID 0000-0001-9282-3415
Sriram VennetiLaboratory of Brain Tumor Metabolism and Epigenetics, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.ORCID 0000-0001-9764-0423
Funding
MICHIGAN MEDICAL SCIENTIST TRAINING PROGRAMT32GM007863 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI COLLINS, KATHLEEN L. · 1985 to 2024
$38.3MThe DNA Damage Response and Tumorigenesis in the BrainP01CA096832 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI BAKER, SUZANNE J. · 2003 to 2025
$38.0MCELLULAR AND MOLECULAR BIOLOGY AT MICHIGANT32GM007315 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PUTHENVEEDU, MANOJKUMAR A · 1985 to 2021
$12.8MTraining Program in Tumor MicroenvironmentT32CA009676 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Maria G Castro, Analisa Virginia DiFeo · 1992 to 2026
$7.3MSynthesizing Image-derived Heterogeneity with Genomic measurements for Assessing Disease Aggressiveness in Lower Grade GliomasR37CA214955 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KURTEK, SEBASTIAN, RAO, ARVIND · 2018 to 2024
$3.9MTargeting Nucleotide Metabolism to Overcome Therapy Resistance in GlioblastomaR37CA258346 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Daniel R Wahl · 2021 to 2026
$3.3MUnravelling metabolic dependencies in H3K27M mutant DIPGR01NS110572 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Sriram Venneti · 2019 to 2026
$2.7MDe Novo Nucleotide Synthesis as a Mediator of Radiation Resistance and a Therapeutic Target in GlioblastomaK08CA234416 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WAHL, DANIEL R · 2019 to 2023
$1.1MTargeting ATRX-Deficient Pediatric GBMK08NS099427 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KOSCHMANN, CARL J · 2017 to 2021
$811kTargeting purine biosynthesis to radiosensitize glioblastomaF32CA260735 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SCOTT, ANDREW JOSEPH · 2021 to 2023
$185kNCI NIH HHS F32 CA260735NCI NIH HHS K08 CA234416NCI NIH HHS P01 CA096832NCI NIH HHS R37 CA214955NCI NIH HHS R37 CA258346NCI NIH HHS T32 CA009676NIGMS NIH HHS T32 GM007315NIGMS NIH HHS T32 GM007863NINDS NIH HHS K08 NS099427NINDS NIH HHS R01 NS110572
Abstract
High-grade gliomas with arginine or valine substitutions of the histone H3.3 glycine-34 residue (H3.3G34R/V) carry a dismal prognosis, and current treatments, including radiotherapy and chemotherapy, are not curative. Because H3.3G34R/V mutations reprogram epigenetic modifications, we undertook a comprehensive epigenetic approach using ChIP sequencing and ChromHMM computational analysis to define therapeutic dependencies in H3.3G34R/V gliomas. Our analyses revealed a convergence of epigenetic alterations, including (i) activating epigenetic modifications on histone H3 lysine (K) residues such as H3K36 trimethylation (H3K36me3), H3K27 acetylation (H3K27ac), and H3K4 trimethylation (H3K4me3); (ii) DNA promoter hypomethylation; and (iii) redistribution of repressive histone H3K27 trimethylation (H3K27me3) to intergenic regions at the
Indexed as
Brain NeoplasmsGliomaAnimalsEpigenesis, GeneticGlycineHistonesHumansMiceGlycineHistones
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