ArticleCancer cell2014
Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition.
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In one paragraph
Article in Cancer cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 437 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
437citing papers in PubMed, 2 pooled it
34.0field-weighted citation impact, top 1% of its field
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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.
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Who cites it
437 citing papers in PubMed, 2 syntheses or guidelines pooled it, 771 citations in OpenAlex.
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- A guideline for the clinical management of basal cell naevus syndrome (Gorlin-Goltz syndrome).The British journal of dermatology · 2022Guideline
- Phase II Study of Vismodegib in Patients WithJCO precision oncology · 2025Trial
- MEVITEM-a phase I/II trial of vismodegib + temozolomide vs temozolomide in patients with recurrent/refractory medulloblastoma with Sonic Hedgehog pathway activation.Neuro-oncology · 2021Trial
- Outcomes by Clinical and Molecular Features in Children With Medulloblastoma Treated With Risk-Adapted Therapy: Results of an International Phase III Trial (SJMB03).Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021Trial
- Paediatric therapeutic development workshop on medulloblastoma.British journal of cancer · 2026Review
- Medulloblastoma-associated mutations in the RNA helicase DDX3X/DED1 cause defects in the translational response to TORC1 inhibition.The Journal of biological chemistry · 2026Article
- Real-world outcomes of radiotherapy timing in infants with medulloblastoma by molecular subtype: a single-center retrospective cohort study.Journal of neuro-oncology · 2026Article
- Therapeutic Potential of Targeting USP2 in Pediatric Group 3 and 4 Medulloblastomas: Insights from In Silico, Ex Vivo, and In Vitro Studies.Cerebellum (London, England) · 2026Article
- From developmental origins to relapse: molecular and therapeutic insights in medulloblastoma.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2026Review
- Dual PI3K/AKT and CDK4/6 inhibition reveals selective sensitivity in an SHH medulloblastoma stem cell model.Molecular oncology · 2026Article
- Differentiation-inducing triiodothyronine enhances chemotherapy and suppresses post-treatment tumor regrowth in medulloblastoma.Molecular therapy. Oncology · 2026Article
- Research progress on the Sonic Hedgehog signaling pathway in the central nervous system: Novel insights.Neural regeneration research · 2026Article
- RAC1 regulates Sonic Hedgehog-medulloblastoma growth via GLI-mediated transcription.Neuro-oncology · 2026Article
- Hedgehog Inhibitor and Paclitaxel: A Phase I Trial of the Oral Hedgehog inhibitor Taladegib in Combination with Weekly Paclitaxel in Patients with Advanced Solid Tumours.Investigational new drugs · 2026Article
- Subtype-specific prognostic impact of TNIK in medulloblastoma.Journal of neuro-oncology · 2026Article
- Article
- Targeted therapies in adolescent and young adult patients with central nervous system tumors.Neuro-oncology advances · 2026Review
- PTEN restrains SHH medulloblastoma growth through cell autonomous and nonautonomous mechanisms.eLife · 2026Article
- Real-world management and long-term outcomes in adolescent, young adult, and adult medulloblastoma: Experience from a monocentric series with multimodal and targeted approaches.Neuro-oncology practice · 2026Article
377 more citing papers are in PubMed but not listed here.
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Authors and funding
77 authors at 20 institutions in 8 countries.
Marcel KoolDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany. Electronic address: m.kool@dkfz.de.
David T W JonesDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.
Natalie JägerDivision of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.
Paul A NorthcottDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.
Trevor J PughBroad Institute of MIT and Harvard, Cambridge, MA 02141, USA.
Volker HovestadtDivision of Molecular Genetics, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.
Rosario M PiroDivision of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.
L Adriana EsparzaSanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.
Shirley L MarkantSanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.
Marc RemkeThe Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON M5G 1L7, Canada.
Till MildeDepartment of Pediatric Oncology, Hematology and Immunology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
Franck BourdeautInstitut Curie, 75005 Paris, France; Institut Curie/INSERM U830, 75248 Paris, France.
Marina RyzhovaDepartment of Neuropathology, NN Burdenko Neurosurgical Institute, Moscow 125047, Russia.
Dominik SturmDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.
Elke PfaffDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.
Sebastian StarkDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.
Sonja HutterDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.
Huriye Seker-CinDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.
Pascal JohannDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.
Sebastian BenderDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.
Christin SchmidtDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.
Tobias RauschEuropean Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany.
David ShihThe Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON M5G 1L7, Canada.
Jüri ReimandThe Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada.
Laura SieberDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.
Andrea WittmannDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.
Linda LinkeDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.
Hendrik WittDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany; Department of Pediatric Oncology, Hematology and Immunology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
Ursula D WeberDivision of Molecular Genetics, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.
Marc ZapatkaDivision of Molecular Genetics, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.
Rainer KönigDivision of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany; Integrated Research and Treatment Center, Center for Sepsis Control and Care, Jena University Hospital, 07747 Jena, Germany; Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute (HKI), 07745 Jena, Germany.
Rameen BeroukhimBroad Institute of MIT and Harvard, Cambridge, MA 02141, USA; Department of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Guillaume BergtholdBroad Institute of MIT and Harvard, Cambridge, MA 02141, USA; Department of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02215, USA; UMR 8203, CNRS Vectorology and Anticancer Therapeutics, Gustave Roussy Cancer Institute, University Paris XI, 94805 Villejuif Cedex, France.
Peter van SluisDepartment of Oncogenomics, Academic Medical Center, Amsterdam 1105 AZ, the Netherlands.
Richard VolckmannDepartment of Oncogenomics, Academic Medical Center, Amsterdam 1105 AZ, the Netherlands.
Jan KosterDepartment of Oncogenomics, Academic Medical Center, Amsterdam 1105 AZ, the Netherlands.
Rogier VersteegDepartment of Oncogenomics, Academic Medical Center, Amsterdam 1105 AZ, the Netherlands.
Sabine SchmidtGenomics and Proteomics Core Facility, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.
Stephan WolfGenomics and Proteomics Core Facility, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.
Chris LawerenzData Management Facility, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.
Cynthia C BartholomaeDivision of Translational Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), 69121 Heidelberg, Germany.
Christof von KalleDivision of Translational Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), 69121 Heidelberg, Germany.
Andreas UnterbergDivision of Translational Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), 69121 Heidelberg, Germany.
Christel Herold-MendeDivision of Translational Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), 69121 Heidelberg, Germany.
Silvia HoferDepartment of Oncology, University Hospital Zürich, 8006 Zürich, Switzerland.
Andreas E KulozikDepartment of Pediatric Oncology, Hematology and Immunology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
Andreas von DeimlingDepartment of Neuropathology, University of Heidelberg, 69120 Heidelberg, Germany; Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.
Wolfram ScheurlenCnopf'sche Kinderklinik, Nürnberg Children's Hospital, 90419 Nürnberg, Germany.
Jörg FelsbergDepartment of Neuropathology, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany.
Guido ReifenbergerDepartment of Neuropathology, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany.
Martin HasselblattInstitute for Neuropathology, University Hospital Münster, 48149 Münster, Germany.
John R CrawfordDepartments of Pediatrics and Neurosciences, University of California San Diego, La Jolla, CA 92093; Rady Children's Hospital, San Diego, CA 92123, USA.
Gerald A GrantDivision of Pediatric Hematology/Oncology, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA; Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Nada JabadoDepartments of Pediatrics and Human Genetics, McGill University Health Centre Research Institute, Montreal, QC H3H 1P3, Canada.
Arie PerryDepartments of Pathology and Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Cynthia CowdreyDepartments of Pathology and Neurological Surgery, Brain Tumor Research Center, University of California, San Francisco, San Francisco, CA 94143, USA.
Sydney CroulDepartment of Neuropathology, The Arthur and Sonia Labatt Brain Tumour Research Centre, Toronto, ON M5G 1L7, Canada.
Gelareh ZadehDepartment of Neuropathology, The Arthur and Sonia Labatt Brain Tumour Research Centre, Toronto, ON M5G 1L7, Canada.
Jan O KorbelEuropean Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany.
Francois DozInstitut Curie, 75005 Paris, France; Université Paris Descartes, 75006 Paris, France.
Olivier DelattreInstitut Curie, 75005 Paris, France; Institut Curie/INSERM U830, 75248 Paris, France.
Gary D BaderThe Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada.
Martin G McCabeManchester Academic Health Science Centre, Manchester M13 9NT, UK.
V Peter CollinsDepartment of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
Mark W KieranPediatric Medical Neuro-Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA 02215, USA.
Yoon-Jae ChoDepartment of Neurology and Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Scott L PomeroyBoston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Olaf WittCCU Pediatric Oncology, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.
Benedikt BrorsDivision of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.
Michael D TaylorThe Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON M5G 1L7, Canada.
Ulrich SchüllerCenter for Neuropathology and Prion Research, Ludwig-Maximilians-Universität, 81377 München, Germany.
Andrey KorshunovDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany; Department of Neuropathology, University of Heidelberg, 69120 Heidelberg, Germany; Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.
Roland EilsDivision of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.
Robert J Wechsler-ReyaSanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.
Peter LichterDivision of Molecular Genetics, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.
Stefan M PfisterDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany; Department of Pediatric Oncology, Hematology and Immunology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
ICGC PedBrain Tumor Project
Heidelberg University · DEGerman Cancer Research Center · DEAcademic Medical Center · NLSanford Burnham Prebys Medical Discovery Institute · USUniversity Hospital Heidelberg · DEBoston Children's Hospital · USEuropean Molecular Biology Laboratory · DEHeinrich Heine University Düsseldorf · DEHospital for Sick Children · CAInserm · FROccupational Cancer Research Centre · CAUniversity of Toronto · CABroad Institute · USBurdenko Neurosurgery Institute · RUCentre National de la Recherche Scientifique · FRCnopf´sche Kinderklinik · DEDana-Farber Cancer Institute · USDuke University Hospital · USInstitut Curie · FRLudwig-Maximilians-Universität München · DE
Funding
GENOMIC ANALYSIS OF MEDULLOBLASTOMASR01CA109467 · NCI · CHILDREN'S HOSPITAL BOSTON · PI MESIROV, JILL P., POMEROY, SCOTT LOREN · 2004 to 2015
$7.3MModulation of the Blood-Tumor Barrier Through Targeted Suppression of Claudin 5K08NS075144 · NINDS · STANFORD UNIVERSITY · PI GRANT, GERALD ARTHUR · 2011 to 2015
$641kNCI NIH HHS R01 CA109467NINDS NIH HHS K08 NS075144
Abstract
Smoothened (SMO) inhibitors recently entered clinical trials for sonic-hedgehog-driven medulloblastoma (SHH-MB). Clinical response is highly variable. To understand the mechanism(s) of primary resistance and identify pathways cooperating with aberrant SHH signaling, we sequenced and profiled a large cohort of SHH-MBs (n = 133). SHH pathway mutations involved PTCH1 (across all age groups), SUFU (infants, including germline), and SMO (adults). Children >3 years old harbored an excess of downstream MYCN and GLI2 amplifications and frequent TP53 mutations, often in the germline, all of which were rare in infants and adults. Functional assays in different SHH-MB xenograft models demonstrated that SHH-MBs harboring a PTCH1 mutation were responsive to SMO inhibition, whereas tumors harboring an SUFU mutation or MYCN amplification were primarily resistant.
Indexed as
AdolescentAdultAnimalsBase SequenceBiphenyl CompoundsCerebellar NeoplasmsChildChild, PreschoolDEAD-box RNA HelicasesDNA Copy Number VariationsDrug Resistance, NeoplasmFemaleGene Expression ProfilingHedgehog ProteinsHigh-Throughput Nucleotide SequencingHumansBiphenyl CompoundsDDX3X protein, humanDEAD-box RNA HelicasesGLI2 protein, humanHedgehog ProteinsKruppel-Like Transcription FactorsMYCN protein, humanN-Myc Proto-Oncogene ProteinNuclear ProteinsOncogene ProteinsPatched-1 ReceptorPatched ReceptorsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktPTCH1 protein, humanPtch1 protein, mousePyridinesReceptors, Cell SurfaceReceptors, G-Protein-CoupledRepressor ProteinsSHH protein, humanSmoothened ReceptorSMO protein, humansonidegibSUFU protein, humanTelomeraseTERT protein, humanTP53 protein, humanTumor Suppressor Protein p53Zinc Finger Protein Gli2
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