ArticleCell2020
Histone H3.3G34-Mutant Interneuron Progenitors Co-opt PDGFRA for Gliomagenesis.
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Article in Cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 2 of them syntheses that pooled it.
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124citing papers in PubMed, 2 pooled it
13.8field-weighted citation impact, top 1% of its field
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Who cites it
124 citing papers in PubMed, 2 syntheses or guidelines pooled it, 187 citations in OpenAlex.
- Contribution of histone variants to aneuploidy: a cancer perspective.Frontiers in genetics · 2023Pooled it
- What are the applications of single-cell RNA sequencing in cancer research: a systematic review.Journal of experimental & clinical cancer research : CR · 2021Pooled it
- Human-specific morphoregulatory signatures in basal radial glia characterise neocortex evolution.Nature communications · 2026Article
- Review
- Histone tail mutants: versatile tools for decoding chromatin, development, and disease.Trends in genetics : TIG · 2026Review
- Potent anti-tumor preclinical efficacy of B7-H3 CAR-T cells in H3G34-mutant, Diffuse Hemispheric Glioma.Neuro-oncology · 2026Article
- Integrated high-resolution copy number and histomolecular analysis of diffuse hemispheric glioma, H3 G34-mutant reveals universal TP53 abnormalities.Brain pathology (Zurich, Switzerland) · 2026Article
- Forebrain Lineage Factor DMRTA2 Is Not Required for Maintenance of H3G34-Mutant Paediatric High-Grade Gliomas.Journal of cellular and molecular medicine · 2026Article
- ATRX inactivation disrupts global chromatin state and topology to dysregulate neurodevelopmental pathways in glioma pathogenesis.Nucleic acids research · 2026Article
- MGMT promoter methylation across glioma subtypes: biological relevance, treatment response, and survival outcomes.Molecular biology reports · 2026Review
- Review
- Clinical Outcomes and Prognostic Features of Diffuse Hemispheric Glioma, H3 G34-Mutant: An International Multi-institutional Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Extracellular Vesicles in the Biology and Liquid Biopsy Diagnostics of Pediatric High-Grade Glioma - Emerging Findings and Opportunities.Journal of extracellular biology · 2026Review
- A longitudinal single-cell and spatial multiomic atlas of pediatric high-grade glioma.Cell reports. Medicine · 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
- Metabolic dependencies and neural progenitor dysregulation: driving forces in paediatric high-grade glioma development.Cancer metastasis reviews · 2026Review
- "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
- Pediatric H3 G34-mutant diffuse hemispheric glioma: clinical, imaging and molecular prognostic factors, MGMT expression, and temozolomide response.Acta neuropathologica · 2026Article
- DMRTA2 Regulates Radial Glial Maintenance and Tumorigenicity of Paediatric High-Grade Glioma.Journal of cellular and molecular medicine · 2026Article
- Development of a Novel Extracellular Vesicle-Based Biomarker Approach for Pediatric High-Grade Glioma.Journal of extracellular biology · 2026Article
64 more citing papers are in PubMed but not listed here.
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Authors and funding
64 authors at 20 institutions in 7 countries.
Carol C L ChenDepartment of Human Genetics, McGill University, Montreal, QC H3A 0C7, Canada.
Shriya DeshmukhDivision of Experimental Medicine, Department of Medicine, McGill University, Montreal, QC H4A 3J1, Canada.
Selin JessaQuantitative Life Sciences, McGill University, Montreal, QC H3A 2A7, Canada; Lady Davis Research Institute, Jewish General Hospital, Montreal, QC H3T 1E2, Canada.
Djihad HadjadjDepartment of Human Genetics, McGill University, Montreal, QC H3A 0C7, Canada.
Véronique LisiDepartment of Human Genetics, McGill University, Montreal, QC H3A 0C7, Canada.
Augusto Faria AndradeDepartment of Human Genetics, McGill University, Montreal, QC H3A 0C7, Canada.
Damien FauryDepartment of Pediatrics, McGill University, and The Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada.
Wajih JawharDepartment of Human Genetics, McGill University, Montreal, QC H3A 0C7, Canada.
Rola DaliCanadian Centre for Computational Genomics, McGill University, Montreal, QC H3A 0E9, Canada.
Hiromichi SuzukiDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Manav PathaniaDepartment of Oncology and The Milner Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; CRUK Children's Brain Tumour Centre of Excellence, University of Cambridge, Cambridge CB2 0RE, UK.
Deli ANuclear Function in CNS Pathophysiology, German Center for Neurodegenerative Diseases (DZNE), Bonn 53127, Germany.
Frank DuboisDana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA, 02215, USA.
Eleanor WoodwardDana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA, 02215, USA.
Steven HébertDepartment of Human Genetics, McGill University, Montreal, QC H3A 0C7, Canada; Lady Davis Research Institute, Jewish General Hospital, Montreal, QC H3T 1E2, Canada.
Marie CoutelierDepartment of Human Genetics, McGill University, Montreal, QC H3A 0C7, Canada; Lady Davis Research Institute, Jewish General Hospital, Montreal, QC H3T 1E2, Canada.
Jason KaramchandaniDepartment of Pathology, Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada.
Steffen AlbrechtDepartment of Pathology, Montreal Children's Hospital, McGill University Health Centre, Montreal, QC H4A 3J1, Canada.
Sebastian BrandnerUCL Queen Square Institute of Neurology, London WC1N 3BG, UK.
Nicolas De JayDepartment of Human Genetics, McGill University, Montreal, QC H3A 0C7, Canada; Lady Davis Research Institute, Jewish General Hospital, Montreal, QC H3T 1E2, Canada.
Tenzin GaydenDepartment of Human Genetics, McGill University, Montreal, QC H3A 0C7, Canada.
Andrea BajicDepartment of Human Genetics, McGill University, Montreal, QC H3A 0C7, Canada.
Ashot S HarutyunyanDepartment of Pediatrics, McGill University, and The Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada.
Dylan M MarchioneDepartment of Biochemistry and Biophysics and Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6073, USA.
Leonie G MikaelDepartment of Pediatrics, McGill University, and The Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada.
Nikoleta JureticDepartment of Pediatrics, McGill University, and The Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada.
Michele ZeiniehDepartment of Human Genetics, McGill University, Montreal, QC H3A 0C7, Canada.
Caterina RussoDepartment of Pediatrics, McGill University, and The Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada.
Nicola MaestroDepartment of Oncology and The Milner Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK.
Angelia V BassendenDepartment of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada.
Peter HauserSecond Department of Paediatrics, Semmelweis University, Budapest 1094, Hungary.
József VirgaDepartment of Neurosurgery, University of Debrecen, Debrecen 4032, Hungary; Department of Oncology, Faculty of Medicine, University of Debrecen, Debrecen 4032, Hungary.
Laszlo BognarDepartment of Neurosurgery, University of Debrecen, Debrecen 4032, Hungary.
Almos KleknerDepartment of Neurosurgery, University of Debrecen, Debrecen 4032, Hungary.
Michal ZapotockyDepartment of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague 150 06, Czech Republic.
Ales VichaDepartment of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague 150 06, Czech Republic.
Lenka KrskovaDepartment of Pathology and Molecular Medicine, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague 150 06, Czech Republic.
Katerina VanovaDepartment of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague 150 06, Czech Republic.
Josef ZamecnikDepartment of Pathology and Molecular Medicine, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague 150 06, Czech Republic.
David SumerauerDepartment of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague 150 06, Czech Republic.
Paul G EkertChildren's Cancer Center, The Royal Children's Hospital; Murdoch Children's Research Institute; Department of Pediatrics, University of Melbourne, Parkville, VIC 3052, Australia.
David S ZieglerKids Cancer Centre, Sydney Children's Hospital, Randwick, NSW 2031, Australia; School of Women's and Children's Health, UNSW Sydney, Kensington, NSW 2052, Australia.
Benjamin EllezamDepartment of Pathology, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montréal, QC H3T 1C5, Canada.
Mariella G FilbinDepartment of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, MA 02215, USA.
Mathieu BlanchetteSchool of Computer Science, McGill University, Montreal, QC H3A 2A7, Canada.
Jordan R HansfordChildren's Cancer Center, The Royal Children's Hospital; Murdoch Children's Research Institute; Department of Pediatrics, University of Melbourne, Parkville, VIC 3052, Australia.
Dong-Anh Khuong-QuangChildren's Cancer Center, The Royal Children's Hospital; and Murdoch Children's Research Institute; Parkville, VIC 3052, Australia.
Albert M BerghuisDepartment of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada.
Alexander G WeilDepartment of Pediatric Neurosurgery, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montréal, QC H3T 1C5, Canada.
Benjamin A GarciaDepartment of Biochemistry and Biophysics and Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6073, USA.
Livia GarziaCancer Research Program, The Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada; Division of Orthopedic Surgery, Faculty of Surgery, McGill University, Montreal, QC H3G 1A4, Canada.
Stephen C MackDepartment of Pediatrics, Division of Hematology and Oncology, Texas Children's Cancer and Hematology Centers, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
Rameen BeroukhimDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215-5450, USA; Broad Institute of MIT and Harvard, Boston, MA 02142, USA.
Keith L LigonDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215-5450, USA; Department of Pathology, Boston Children's Hospital and Brigham and Women's Hospital, Harvard Medical School, and Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Michael D TaylorDevelopmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Pratiti BandopadhayayDana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA, 02215, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215-5450, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Christoph KrammDivision of Pediatric Hematology and Oncology, University Medical Center Goettingen, Goettingen 37075, Germany.
Stefan M PfisterHopp Children's Cancer Center Heidelberg (KiTZ) and Department of Pediatric Oncology, Hematology and Immunology, University Hospital Heidelberg, Heidelberg 69120, Germany; Division of Pediatric Neurooncology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg 69120, Germany; Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg 69120, Germany.
Andrey KorshunovDepartment of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg 69120, Germany; Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
Dominik SturmDivision of Pediatric Hematology and Oncology, University Medical Center Goettingen, Goettingen 37075, Germany; Pediatric Glioma Research Group, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
David T W JonesClinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg 69120, Germany; Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg 69120, Germany.
Paolo SalomoniDepartment of Oncology and The Milner Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; Nuclear Function in CNS Pathophysiology, German Center for Neurodegenerative Diseases (DZNE), Bonn 53127, Germany.
Claudia L KleinmanDepartment of Human Genetics, McGill University, Montreal, QC H3A 0C7, Canada; Lady Davis Research Institute, Jewish General Hospital, Montreal, QC H3T 1E2, Canada. Electronic address: claudia.kleinman@mcgill.ca.
Nada JabadoDepartment of Human Genetics, McGill University, Montreal, QC H3A 0C7, Canada; Division of Experimental Medicine, Department of Medicine, McGill University, Montreal, QC H4A 3J1, Canada; Department of Pediatrics, McGill University, and The Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada. Electronic address: nada.jabado@mcgill.ca.
McGill University · CAMcGill University Health Centre · CACharles University · CZJewish General Hospital · CAGerman Cancer Research Center · DEDana-Farber/Boston Children's Cancer and Blood Disorders Center · USRoyal Children's Hospital · AUUniversity of Debrecen · HUCentre Hospitalier Universitaire Sainte-Justine · CAGerman Center for Neurodegenerative Diseases · DEHospital for Sick Children · CAUniversity of Cambridge · GBUniversity of Pennsylvania · USBaylor College of Medicine · USBrigham and Women's Hospital · USBroad Institute · USHarvard University · USMontreal Children's Hospital · CAMontreal Neurological Institute and Hospital · CANational Hospital for Neurology and Neurosurgery · GB
Funding
Targeting the Vasular SystemP50CA165962 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Benjamin Harris Kann · 2013 to 2026
$33.5MShared Resources Core 2: Quantitative Proteomics CoreP01CA196539 · NCI · ROCKEFELLER UNIVERSITY · PI MUIR, TOM · 2015 to 2024
$17.6MYNG1 PHD BINDING TO H3 3METHYL AT K4 PROMOTES TRANSCRIPTION AT TARGETED ORFSP41RR000862 · NCRR · ROCKEFELLER UNIVERSITY · PI DARNELL, JAMES E · 1985 to 2011
$16.1MMouse models to discover new drivers of medulloblastomaR01CA159859 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI Michael D. Taylor, WILLIAM A WEISS · 2011 to 2026
$10.4MMYB family alterations in pediatric gliomasR01CA215489 · NCI · DANA-FARBER CANCER INST · PI BEROUKHIM, RAMEEN, LIGON, KEITH LLOYD · 2017 to 2021
$2.8MCharacterizing TP53 and PPM1D mutations as resistance drivers to radiation therapy in Diffuse Intrinsic Pontine GliomasR01CA219943 · NCI · BROAD INSTITUTE, INC. · PI BEROUKHIM, RAMEEN, LIGON, KEITH LLOYD · 2017 to 2021
$2.5MMedulloblastoma and MetastasesR01CA148699 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI TAYLOR, MICHAEL D., WEISS, WILLIAM A · 2010 to 2014
$2.4MCharacterizing the resistance mechanisms to BET-bromodomain inhibition in MYC-amplified medulloblastomaR00CA201592 · NCI · DANA-FARBER CANCER INST · PI BANDOPADHAYAY, PRATITI · 2018 to 2020
$697kCIHR FDN-154307CIHR MOP-286756CIHR PJT-156086Medical Research Council MR/M00094X/1NCI NIH HHS P01 CA196539NCI NIH HHS P50 CA165962NCI NIH HHS R00 CA201592NCI NIH HHS R01 CA148699NCI NIH HHS R01 CA159859NCI NIH HHS R01 CA215489NCI NIH HHS R01 CA219943NCRR NIH HHS P41 RR000862
Abstract
Histone H3.3 glycine 34 to arginine/valine (G34R/V) mutations drive deadly gliomas and show exquisite regional and temporal specificity, suggesting a developmental context permissive to their effects. Here we show that 50% of G34R/V tumors (n = 95) bear activating PDGFRA mutations that display strong selection pressure at recurrence. Although considered gliomas, G34R/V tumors actually arise in GSX2/DLX-expressing interneuron progenitors, where G34R/V mutations impair neuronal differentiation. The lineage of origin may facilitate PDGFRA co-option through a chromatin loop connecting PDGFRA to GSX2 regulatory elements, promoting PDGFRA overexpression and mutation. At the single-cell level, G34R/V tumors harbor dual neuronal/astroglial identity and lack oligodendroglial programs, actively repressed by GSX2/DLX-mediated cell fate specification. G34R/V may become dispensable for tumor maintenance, whereas mutant-PDGFRA is potently oncogenic. Collectively, our results open novel research avenues in deadly tumors. G34R/V gliomas are neuronal malignancies where interneuron progenitors are stalled in differentiation by G34R/V mutations and malignant gliogenesis is promoted by co-option of a potentially targetable pathway, PDGFRA signaling.
Indexed as
AnimalsAstrocytesBrain NeoplasmsCarcinogenesisCell LineageCellular ReprogrammingChromatinEmbryo, MammalianEpigenesis, GeneticGene Expression Regulation, NeoplasticGene SilencingGliomaHistonesInterneuronsLysineMice, Inbred C57BLChromatinHistonesLysineReceptor, Platelet-Derived Growth Factor alphacell-of-originchromatin conformationgliomasGSX2H3.3 G34R/Vinterneuron progenitorsoncohistonesPDGFRApediatric cancersingle-cell transcriptome
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