ArticleNature genetics2014
Recurrent somatic mutations in ACVR1 in pediatric midline high-grade astrocytoma.
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Article in Nature genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 267 papers, 3 of them syntheses that pooled it.
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267citing papers in PubMed, 3 pooled it
26.8field-weighted citation impact, top 1% of its field
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Who cites it
267 citing papers in PubMed, 3 syntheses or guidelines pooled it, 461 citations in OpenAlex.
- The clinicopathological and prognostic significance of TP53 alteration in K27M mutated gliomas: an individual-participant data meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2018Pooled it
- Reconstructing the molecular life history of gliomas.Acta neuropathologica · 2018Pooled it
- Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma.Cancer cell · 2017Pooled it
- A phase I/II study of ribociclib following radiation therapy in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG).Journal of neuro-oncology · 2020Trial
- High-throughput spheroid profiling reveals BMP-driven rewiring of glioma cell death responses.bioRxiv : the preprint server for biology · 2026Article
- Understanding DMG: current treatment options and prospective solutions using nanoparticles.Drug delivery and translational research · 2026Review
- Clinical Impact of Germline Multigene Sequencing in Pediatric Cohorts with a Wide Spectrum of Neoplasms.International journal of molecular sciences · 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
- Feasibility of long-read nanopore sequencing for methylation-based classification of posterior fossa ependymomas.Brain tumor pathology · 2026Article
- Efficacy of chemoradiotherapy in pediatric H3K27M-mutant diffuse intrinsic pontine glioma: a study based on single-center and SEER data.Journal of neuro-oncology · 2026Article
- Nanopore and EPIC array profiling unmask an atypical non-midline H3 K27-altered glioma: a case report.Frontiers in oncology · 2026Article
- OncogenicbioRxiv : the preprint server for biology · 2025Article
- Molecular characterization and clinical features of diffuse midline glioma in the pediatric precision oncology registry INFORM.Acta neuropathologica · 2025Article
- Germline analysis of an international cohort of pediatric diffuse midline glioma patients.Neuro-oncology · 2025Article
- Single-Cell Profiling of Pediatric High-Grade Gliomas Reveals OPC-Like Subpopulations Driving Tumorigenic Lineage Transitions.Pediatric discovery · 2025Article
- A specific form of cPRC1 containing CBX4 is co-opted to mediate oncogenic gene repression in diffuse midline glioma.Molecular cell · 2025Article
- An oncohistone-driven H3.3K27M/CREB5/ID1 axis maintains the stemness and malignancy of diffuse intrinsic pontine glioma.Nature communications · 2025Article
- H3 K27M mutation in rosette-forming glioneuronal tumors: a potential diagnostic pitfall.Virchows Archiv : an international journal of pathology · 2025Article
- Aberrant histone modifications in pediatric brain tumors.Frontiers in oncology · 2025Review
- Histone H3 mutations and their impact on genome stability maintenance.Biochemical Society transactions · 2024Review
207 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
48 authors at 20 institutions in 5 countries.
Adam M Fontebasso1] Division of Experimental Medicine, Montreal Children's Hospital, McGill University and McGill University Health Centre, Montreal, Quebec, Canada. [2].
Simon Papillon-Cavanagh1] Department of Human Genetics, McGill University, Montreal, Quebec, Canada. [2].
Jeremy Schwartzentruber1] Wellcome Trust Sanger Institute, Hinxton, UK. [2].
Hamid NikbakhtDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.
Noha GergesDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.
Pierre-Olivier FisetDepartment of Pathology, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
Denise BechetDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.
Damien Faury1] Department of Human Genetics, McGill University, Montreal, Quebec, Canada. [2] Department of Pediatrics, McGill University, Montreal, Quebec, Canada.
Nicolas De JayDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.
Lori A RamkissoonDepartment of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Aoife CorcoranDepartment of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
David T W JonesDivision of Pediatric Neuro-oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Dominik SturmDivision of Pediatric Neuro-oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Pascal JohannDivision of Pediatric Neuro-oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Tadanori TomitaDepartment of Neurological Surgery, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University, Chicago, Illinois, USA.
Stewart GoldmanDepartment of Pediatrics Hematology-Oncology, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University, Chicago, Illinois, USA.
Mahmoud NagibClinical Pediatric Neurosurgical Oncology, Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, USA.
Anne BendelDepartment of Pediatric Hematology-Oncology, Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota, USA.
Liliana Goumnerova1] Department of Neurosurgery, Boston Children's Hospital, Boston, Massachusetts, USA. [2] Harvard Medical School, Boston, Massachusetts, USA.
Daniel C BowersDepartment of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Jeffrey R LeonardDepartment of Neurological Surgery, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.
Joshua B RubinDepartment of Pediatrics, Hematology-Oncology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.
Tord AldenDepartment of Neurological Surgery, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University, Chicago, Illinois, USA.
Samuel BrowdDepartment of Neurosurgery, Seattle Children's Hospital, Seattle, Washington, USA.
J Russell GeyerCancer and Blood Disorders Center, Seattle Children's Hospital, Seattle, Washington, USA.
Sarah LearyCancer and Blood Disorders Center, Seattle Children's Hospital, Seattle, Washington, USA.
George JalloDepartment of Neurological Surgery, Johns Hopkins Hospital, Baltimore, Maryland, USA.
Kenneth CohenDepartment of Pediatric Hematology-Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA.
Nalin GuptaDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Michael D PradosDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Anne-Sophie CarretDepartment of Hematology-Oncology, Centre Hospitalier Universitaire (CHU) Sainte-Justine, Université de Montréal, Montreal, Quebec, Canada.
Benjamin EllezamDepartment of Pathology, Centre Hospitalier Universitaire (CHU) Sainte-Justine, Université de Montréal, Montreal, Quebec, Canada.
Louis CrevierDepartment of Neurosurgery, Centre Hospitalier Universitaire (CHU) Sainte-Justine, Université de Montréal, Montreal, Quebec, Canada.
Almos KleknerDepartment of Neurosurgery, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
Laszlo BognarDepartment of Neurosurgery, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
Peter Hauser2nd Department of Paediatrics, Semmelweis University, Budapest, Hungary.
Miklos Garami2nd Department of Paediatrics, Semmelweis University, Budapest, Hungary.
John MyserosDepartment of Neurosurgery, Children's National Medical Center, Washington, DC, USA.
Zhifeng DongRosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.
Peter M SiegelRosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.ORCID 0000000255686586
Hayley MalkinDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Azra H Ligon1] Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [2] Harvard Medical School, Boston, Massachusetts, USA. [3] Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Steffen AlbrechtDepartment of Pathology, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
Stefan M PfisterDivision of Pediatric Neuro-oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Keith L Ligon1] Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [2] Harvard Medical School, Boston, Massachusetts, USA. [3] Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA. [4] Department of Pathology, Boston Children's Hospital, Boston, Massachusetts, USA. [5].
Jacek Majewski1] Department of Human Genetics, McGill University, Montreal, Quebec, Canada. [2].
Nada Jabado1] Division of Experimental Medicine, Montreal Children's Hospital, McGill University and McGill University Health Centre, Montreal, Quebec, Canada. [2] Department of Human Genetics, McGill University, Montreal, Quebec, Canada. [3] Department of Pediatrics, McGill University, Montreal, Quebec, Canada. [4].
Mark W Kieran1] Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [3] Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, Massachusetts, USA. [4].
McGill University · CAGerman Cancer Research Center · DEMontreal Children's Hospital · CABoston Children's Hospital · USCentre Hospitalier Universitaire Sainte-Justine · CADana-Farber Cancer Institute · USNorthwestern University · USSeattle Children's Hospital · USBrigham and Women's Hospital · USMcGill Genome Centre · CAMcGill University Health Centre · CASemmelweis University · HUUniversity of California, San Francisco · USUniversity of Debrecen · HUWashington University in St. Louis · USChildren's Minnesota · USChildren's National · USJohns Hopkins Hospital · USSidney Kimmel Comprehensive Cancer Center · USThe University of Texas Southwestern Medical Center · US
Funding
Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Daniela E Matei · 1993 to 2026
$153.9MTherapeutic Opportunities for Pediatric AstrocytomaP01CA142536 · NCI · DANA-FARBER CANCER INST · PI SEGAL, ROSALIND A. · 2011 to 2015
$7.9MCIHRNCI NIH HHS P01 CA142536NCI NIH HHS P30 CA060553
Abstract
Pediatric midline high-grade astrocytomas (mHGAs) are incurable with few treatment targets identified. Most tumors harbor mutations encoding p.Lys27Met in histone H3 variants. In 40 treatment-naive mHGAs, 39 analyzed by whole-exome sequencing, we find additional somatic mutations specific to tumor location. Gain-of-function mutations in ACVR1 occur in tumors of the pons in conjunction with histone H3.1 p.Lys27Met substitution, whereas FGFR1 mutations or fusions occur in thalamic tumors associated with histone H3.3 p.Lys27Met substitution. Hyperactivation of the bone morphogenetic protein (BMP)-ACVR1 developmental pathway in mHGAs harboring ACVR1 mutations led to increased levels of phosphorylated SMAD1, SMAD5 and SMAD8 and upregulation of BMP downstream early-response genes in tumor cells. Global DNA methylation profiles were significantly associated with the p.Lys27Met alteration, regardless of the mutant histone H3 variant and irrespective of tumor location, supporting the role of this substitution in driving the epigenetic phenotype. This work considerably expands the number of potential treatment targets and further justifies pretreatment biopsy in pediatric mHGA as a means to orient therapeutic efforts in this disease.
Indexed as
Activin Receptors, Type IAnimalsAstrocytomaBase SequenceBone Morphogenetic ProteinsBrain NeoplasmsChildDNA Copy Number VariationsDNA MethylationGene Expression Regulation, NeoplasticGenome, HumanHumansImmunohistochemistryIn Situ Hybridization, FluorescenceMolecular Sequence DataMutationActivin Receptors, Type IACVR1 protein, humanBone Morphogenetic ProteinsSmad Proteins
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