ArticleCancer discovery2020
H3.3 G34W Promotes Growth and Impedes Differentiation of Osteoblast-Like Mesenchymal Progenitors in Giant Cell Tumor of Bone.
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Article in Cancer discovery, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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50citing papers in PubMed
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50 citing papers in PubMed, 73 citations in OpenAlex.
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- Extracellular Vesicles in the Biology and Liquid Biopsy Diagnostics of Pediatric High-Grade Glioma - Emerging Findings and Opportunities.Journal of extracellular biology · 2026Review
- Establishment and characterization of NCC-GCTB16-C1: novel patient-derived cell line of giant cell tumor of bone.Human cell · 2026Article
- Giant Cell Tumor of Bone: Biology, Pathophysiology, and Histopathology in the Era of H3F3A.Biomedicines · 2026Review
- Research advances in the role of osteoblasts and their derivatives in the development, recurrence, and distant metastasis of malignant bone tumors: a narrative review.EFORT open reviews · 2025Review
- Nicheformer: a foundation model for single-cell and spatial omics.Nature methods · 2025Article
- Soft tissue recurrence in giant cell tumor of Bone: A comprehensive review of pathogenesis, imaging features, and clinical management.Journal of bone oncology · 2025Review
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- Aberrant EZHIP expression drives tumorigenesis in osteosarcoma.Nature communications · 2025Article
- Role of epigenetics in paediatric cancer pathogenesis & drug resistance.British journal of cancer · 2025Review
- Molecular pathological insights into tumorigenesis and progression of giant cell tumor of bone.Journal of bone oncology · 2025Review
- Histone H3E50K remodels chromatin to confer oncogenic activity and support an EMT phenotype.NAR cancer · 2025Article
- IDH1/2 Mutations in Cancer: Unifying Insights and Unlocking Therapeutic Potential for Chondrosarcoma.Targeted oncology · 2025Review
- (B)On(e)-cohistones and the epigenetic alterations at the root of bone cancer.Cell death and differentiation · 2025Review
- Genome-wide chromosome architecture prediction reveals biophysical principles underlying gene structure.Cell genomics · 2024Article
- H3.3-G34W in giant cell tumor of bone functionally aligns with the exon choice repressor hnRNPA1L2.Cancer gene therapy · 2024Article
- The tumor-stroma ratio in giant cell tumor of bone: associations with the immune microenvironment and responsiveness to denosumab treatment.Journal of orthopaedic surgery and research · 2024Article
- Cancer-associated Histone H3 N-terminal arginine mutations disrupt PRC2 activity and impair differentiation.Nature communications · 2024Article
- Current Concepts in the Treatment of Giant Cell Tumor of Bone: An Update.Current oncology (Toronto, Ont.) · 2024Review
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Authors and funding
31 authors at 12 institutions in 3 countries.
Sima Khazaei *Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
Nicolas De Jay *Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
Shriya Deshmukh *Department of Experimental Medicine, McGill University, Montreal, Quebec, Canada.
Liam D Hendrikse *Cancer and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.ORCID https://orcid.org/0000-0002-0253-8512
Wajih JawharDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.ORCID https://orcid.org/0000-0002-2724-6401
Carol C L ChenDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.
Leonie G MikaelDepartment of Pediatrics, McGill University, and The Research Institute of the McGill University Health Center, Montreal, Quebec, Canada.
Damien FauryDepartment of Pediatrics, McGill University, and The Research Institute of the McGill University Health Center, Montreal, Quebec, Canada.
Dylan M MarchioneDepartment of Biochemistry and Biophysics, and Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.ORCID https://orcid.org/0000-0001-6941-0604
Joel LanoixInstitute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, Quebec, Canada.
Éric BonneilInstitute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, Quebec, Canada.ORCID https://orcid.org/0000-0002-4039-3131
Takeaki IshiiCancer Research Program, The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
Siddhant U JainDepartment of Biomolecular Chemistry, School of Medicine and Public Health and Wisconsin Institute for Discovery, University of Wisconsin, Madison, Wisconsin.ORCID https://orcid.org/0000-0002-7390-6757
Kateryna RossokhataDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.
Tianna S SihotaDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.ORCID https://orcid.org/0000-0002-5433-1900
Robert EveleighMcGill University and Génome Québec Innovation Centre, Montreal, Quebec, Canada.ORCID https://orcid.org/0000-0002-4147-382X
Véronique LisiDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.ORCID https://orcid.org/0000-0001-5385-4219
Ashot S HarutyunyanDepartment of Pediatrics, McGill University, and The Research Institute of the McGill University Health Center, Montreal, Quebec, Canada.
Sungmi JungDepartment of Pathology, McGill University Health Centre, Montreal, Quebec, Canada.
Jason KaramchandaniDepartment of Pathology, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
Brendan C DicksonDepartment of Pathology and Laboratory Medicine, Mt. Sinai Hospital, Toronto, Ontario, Canada.ORCID https://orcid.org/0000-0003-2269-6216
Robert TurcotteDivision of Orthopaedic Surgery, McGill University, Montreal, Quebec, Canada.
Jay S WunderUniversity of Toronto Musculoskeletal Oncology Unit, Mount Sinai Hospital, Toronto, Ontario, Canada.ORCID https://orcid.org/0000-0002-5978-9400
Pierre ThibaultInstitute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, Quebec, Canada.
Peter W LewisDepartment of Biomolecular Chemistry, School of Medicine and Public Health and Wisconsin Institute for Discovery, University of Wisconsin, Madison, Wisconsin.ORCID https://orcid.org/0000-0002-9816-7823
Benjamin A GarciaDepartment of Biochemistry and Biophysics, and Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
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, Texas.
Michael D TaylorCancer and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
Livia GarziaCancer Research Program, The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
Claudia L KleinmanDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada. nada.jabado@mcgill.ca claudia.kleinman@mcgill.ca.
Nada JabadoDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada. nada.jabado@mcgill.ca claudia.kleinman@mcgill.ca.
McGill University Health Centre · CAMcGill Genome Centre · CAInstitute for Research in Immunology and Cancer · CAJewish General Hospital · CAMcGill University · CAMount Sinai Hospital · CAUniversity of Pennsylvania · USUniversity of Toronto · CAWisconsin Institutes for Discovery · USChildren's Cancer Center · USMcGill University and Génome Québec Innovation Centre · CAMontreal Neurological Institute and Hospital · CA
Funding
Shared 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 FENYO, DAVID · 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
$10.4MMedulloblastoma and MetastasesR01CA148699 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI TAYLOR, MICHAEL D., WEISS, WILLIAM A · 2010 to 2014
$2.4MNCI NIH HHS P01 CA196539NCI NIH HHS R01 CA148699NCI NIH HHS R01 CA159859NCRR NIH HHS P41 RR000862
Abstract
Glycine 34-to-tryptophan (G34W) substitutions in H3.3 arise in approximately 90% of giant cell tumor of bone (GCT). Here, we show H3.3 G34W is necessary for tumor formation. By profiling the epigenome, transcriptome, and secreted proteome of patient samples and tumor-derived cells CRISPR-Cas9-edited for H3.3 G34W, we show that H3.3K36me3 loss on mutant H3.3 alters the deposition of the repressive H3K27me3 mark from intergenic to genic regions, beyond areas of H3.3 deposition. This promotes redistribution of other chromatin marks and aberrant transcription, altering cell fate in mesenchymal progenitors and hindering differentiation. Single-cell transcriptomics reveals that H3.3 G34W stromal cells recapitulate a neoplastic trajectory from a
Indexed as
Bone NeoplasmsCell DifferentiationGiant Cell Tumor of BoneHumansMesenchymal Stem CellsOsteoblasts
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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.