ArticleNature genetics2014
Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations.
Registry-linked trialOpen access · greenAbstract read
In one paragraph
Article in Nature genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01106794 (Molecular Analysis of Samples From Patients With Diffuse Intrinsic Pontine Glioma and Brainstem Glioma), which is not on this map. Cited by 362 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
362citing papers in PubMed, 2 pooled it
34.8field-weighted citation impact, top 1% of its field
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.
Molecular Analysis of Samples From Patients With Diffuse Intrinsic Pontine Glioma and Brainstem Glioma
Who cites it
362 citing papers in PubMed, 2 syntheses or guidelines pooled it, 649 citations in OpenAlex.
- Contribution of histone variants to aneuploidy: a cancer perspective.Frontiers in genetics · 2023Pooled it
- Prognostic Implication of Patient Age in H3K27M-Mutant Midline Gliomas.Frontiers in oncology · 2022Pooled it
- Phase I/II trial of vorinostat and radiation and maintenance vorinostat in children with diffuse intrinsic pontine glioma: A Children's Oncology Group report.Neuro-oncology · 2022Trial
- 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
- AOSNP-ADAPTR resource level-based recommendations on practical diagnostic strategies for ependymomas.Brain pathology (Zurich, Switzerland) · 2026Article
- Article
- High-throughput spheroid profiling reveals BMP-driven rewiring of glioma cell death responses.bioRxiv : the preprint server for biology · 2026Article
- A novel combinatorial therapeutic strategy using resveratrol and viral oncolysis for diffuse intrinsic pontine glioma: an in vitro study.3 Biotech · 2026Article
- Clinical, molecular, and surgical predictors of outcome in non-DIPG pediatric diffuse midline gliomas: A collaborative retrospective analysis.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2026Article
- Reirradiation for diffuse intrinsic pontine glioma in an upper middle-income country: does full dose improve outcomes?Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2026Observational
- Potent anti-tumor preclinical efficacy of B7-H3 CAR-T cells in H3G34-mutant, Diffuse Hemispheric Glioma.Neuro-oncology · 2026Article
- A pontine-specific niche supports de novo gliomagenesis.Cell reports · 2026Article
- A perfused, parallelized blood brain barrier-tumor platform for compound permeation and efficacy investigations.Microsystems & nanoengineering · 2026Article
- Systematic design of combination therapy by targeting master regulators of coexisting diffuse midline glioma cell states.Nature genetics · 2026Article
- Co-detection of mutations and methylations in cerebrospinal fluid ctdna for minimally-invasive diagnosis of brainstem glioma.Journal of experimental & clinical cancer research : CR · 2025Article
- Germline analysis of an international cohort of pediatric diffuse midline glioma patients.Neuro-oncology · 2025Article
- The proteomic landscape of diffuse midline glioma highlights the therapeutic potential of non-histone protein methyltransferases.Neuro-oncology · 2025Article
- Operative performance of RAPNO DIPG imaging criteria-a study from the International DIPG/DMG Registry.Neuro-oncology practice · 2025Article
- Current Landscape of Preclinical Models for Pediatric Gliomas: Clinical Implications and Future Directions.Cancers · 2025Review
- Dual treatment with Val-083 and AZD1775 shows potent anti-tumor activity in diffuse midline glioma models.NPJ precision oncology · 2025Article
302 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
52 authors at 20 institutions in 4 countries.
Pawel Buczkowicz1] Division of Pathology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. [2] Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada. [3] Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. [4].
Christine Hoeman1] Division of Pediatric Hematology/Oncology, Duke University Medical Center, Durham, North Carolina, USA. [2].
Patricia Rakopoulos1] Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada. [2] Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Sanja PajovicArthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
Louis LetourneauGénome Québec Innovation Centre, McGill University, Montreal, Quebec, Canada.
Misko DzambaDepartment of Computer Science, University of Toronto, Toronto, Ontario, Canada.
Andrew MorrisonArthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
Peter LewisLaboratory of Chromatin Biology and Epigenetics, Rockefeller University, New York, New York, USA.
Eric BouffetDivision of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Ute BartelsDivision of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Jennifer ZuccaroArthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
Sameer AgnihotriArthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
Scott RyallArthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
Mark Barszczyk1] Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada. [2] Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Yevgen Chornenkyy1] Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada. [2] Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Mathieu BourgeyGénome Québec Innovation Centre, McGill University, Montreal, Quebec, Canada.
Guillaume BourqueGénome Québec Innovation Centre, McGill University, Montreal, Quebec, Canada.
Alexandre MontpetitGénome Québec Innovation Centre, McGill University, Montreal, Quebec, Canada.
Francisco CorderoDivision of Pediatric Hematology/Oncology, Duke University Medical Center, Durham, North Carolina, USA.
Pedro Castelo-BrancoArthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
Joshua MangerelArthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
Uri Tabori1] Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada. [2] Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada.
King Ching HoArthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
Annie Huang1] Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada. [2] Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Kathryn R TaylorDivision of Cancer Therapeutics, Institute of Cancer Research, London, UK.
Alan MackayDivision of Cancer Therapeutics, Institute of Cancer Research, London, UK.
Anne E BendelDepartment of Pediatric Hematology-Oncology, Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota, USA.
Javad NazarianCenter for Genetic Medicine, Children's National Medical Center, Washington, DC, USA.
Jason R FangusaroDepartment of Pediatrics-Hematology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.
Matthias A KarajannisDivision of Pediatric Hematology/Oncology and Neuropathology, New York University Cancer Institute, New York University Langone Medical Center, New York, New York, USA.
David ZagzagDivision of Pediatric Hematology/Oncology and Neuropathology, New York University Cancer Institute, New York University Langone Medical Center, New York, New York, USA.
Nicholas K ForemanDepartment of Pediatrics, Children's Hospital Colorado, Denver, Colorado, USA.
Andrew DonsonDepartment of Pediatrics, Children's Hospital Colorado, Denver, Colorado, USA.
Julia V HegertDepartment of Pathology, Arnold Palmer Hospital for Children, Orlando, Florida, USA.
Amy SmithDepartment of Pathology, Arnold Palmer Hospital for Children, Orlando, Florida, USA.
Jennifer ChanClark H. Smith Brain Tumour Centre, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
Lucy Lafay-CousinClark H. Smith Brain Tumour Centre, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
Sandra DunnDepartment of Pediatric Neurology and Neuro-Oncology, BC Children's Hospital, Vancouver, British Columbia, Canada.
Juliette HukinDepartment of Pediatric Neurology and Neuro-Oncology, BC Children's Hospital, Vancouver, British Columbia, Canada.
Chris DunhamDepartment of Pediatric Neurology and Neuro-Oncology, BC Children's Hospital, Vancouver, British Columbia, Canada.
Katrin ScheinemannDivision of Hematology/Oncology, McMaster Children's Hospital, Hamilton, Ontario, Canada.
Jean MichaudDepartment of Pathology and Laboratory Medicine, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
Shayna ZelcerDepartment of Hematology/Oncology, Children's Hospital London Health Sciences Centre, London, Ontario, Canada.
David RamsayDepartment of Hematology/Oncology, Children's Hospital London Health Sciences Centre, London, Ontario, Canada.
Jason CainMonash Institute of Medical Research, Monash Medical Centre, Clayton, Victoria, Australia.
Cameron BrennanDepartment of Neurological Surgery, Weill Cornell Medical College and Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Mark M SouweidaneDepartment of Neurological Surgery, Weill Cornell Medical College and Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Chris JonesDivision of Cancer Therapeutics, Institute of Cancer Research, London, UK.
C David AllisLaboratory of Chromatin Biology and Epigenetics, Rockefeller University, New York, New York, USA.
Michael Brudno1] Department of Computer Science, University of Toronto, Toronto, Ontario, Canada. [2] The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.
Oren Becher1] Division of Pediatric Hematology/Oncology, Duke University Medical Center, Durham, North Carolina, USA. [2].
Cynthia Hawkins1] Division of Pathology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. [2] Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada. [3] Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. [4].
Hospital for Sick Children · CASickKids Foundation · CAMcGill University and Génome Québec Innovation Centre · CAUniversity of Toronto · CABritish Columbia Children's Hospital · CADuke Medical Center · USInstitute of Cancer Research · GBArnold Palmer Hospital for Children · USLondon Health Sciences Centre · CANYU Langone Health · USRockefeller University · USUniversity of Calgary · CAChildren's Hospital Colorado · USChildren's Hospital of Eastern Ontario · CAChildren's Minnesota · USChildren's National · USCornell University · USLurie Children's Hospital · USMcMaster Children's Hospital · CAMemorial Sloan Kettering Cancer Center · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MWomen's Cancer Research ProgramP30CA014236 · NCI · DUKE UNIVERSITY · PI DONNA NIEDZWIECKI · 1985 to 2026
$174.8MTumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Daniela E Matei · 1993 to 2026
$153.9MVaccine FacilityP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ADRIANA HEGUY · 1985 to 2026
$83.1MInstitutional Clinical and Translational Science AwardUL1TR000038 · NCATS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI CRONSTEIN, BRUCE NEIL, HOCHMAN, JUDITH S · 2012 to 2014
$16.8MTraining Program in Developmental & Stem Cell BiologyT32HD040372 · NICHD · DUKE UNIVERSITY · PI Terry H Lechler · 2001 to 2026
$8.9MCIHR 115004-1CIHR MOP 115004NCATS NIH HHS UL1 TR000038NCATS NIH HHS UL1TR000038NCI NIH HHS 5P30CA016087-32NCI NIH HHS P30 CA016087
Abstract
Diffuse intrinsic pontine glioma (DIPG) is a fatal brain cancer that arises in the brainstem of children, with no effective treatment and near 100% fatality. The failure of most therapies can be attributed to the delicate location of these tumors and to the selection of therapies on the basis of assumptions that DIPGs are molecularly similar to adult disease. Recent studies have unraveled the unique genetic makeup of this brain cancer, with nearly 80% found to harbor a p.Lys27Met histone H3.3 or p.Lys27Met histone H3.1 alteration. However, DIPGs are still thought of as one disease, with limited understanding of the genetic drivers of these tumors. To understand what drives DIPGs, we integrated whole-genome sequencing with methylation, expression and copy number profiling, discovering that DIPGs comprise three molecularly distinct subgroups (H3-K27M, silent and MYCN) and uncovering a new recurrent activating mutation affecting the activin receptor gene ACVR1 in 20% of DIPGs. Mutations in ACVR1 were constitutively activating, leading to SMAD phosphorylation and increased expression of the downstream activin signaling targets ID1 and ID2. Our results highlight distinct molecular subgroups and novel therapeutic targets for this incurable pediatric cancer.
Indexed as
Activin Receptors, Type IAnimalsBrain Stem NeoplasmsChildDNA Copy Number VariationsDNA MethylationGene Expression ProfilingGene Expression Regulation, NeoplasticGenome, HumanGliomaHumansInhibitor of Differentiation Protein 1Inhibitor of Differentiation Protein 2PhosphorylationSequence Analysis, DNASmad ProteinsActivin Receptors, Type IACVR1 protein, humanID1 protein, humanID2 protein, humanInhibitor of Differentiation Protein 1Inhibitor of Differentiation Protein 2Smad Proteins
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Registered trials
NCT01106794ClinicalTrials.gov
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.