ArticleNature2014
Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma.
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Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 417 papers.
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417citing papers in PubMed
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417 citing papers in PubMed, 668 citations in OpenAlex.
- Identification of Genome-Wide Chromatin Structural Aberration in Cancer by Hi-C Analysis.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Paediatric therapeutic development workshop on medulloblastoma.British journal of cancer · 2026Review
- Origins and consequences of oncogenic 3D chromatin remodelling.Nature reviews. Cancer · 2026Review
- The molecular heterogeneity and clinical impact of genomic driver alterations in prostate cancer.Nature communications · 2026Article
- Divergent medulloblastoma chromatin states disclose KDM2B as a selective dependency.Nature genetics · 2026Article
- Epigenetic reprogramming of lineage switching in cancer.FEBS letters · 2026Review
- CReP-mediated control of eIF2α phosphorylation is a critical node in MYC-driven medulloblastoma.Nature communications · 2026Article
- Cancer-associated KBTBD4 mutations induce differentiation defects and confer a unique therapeutic vulnerability.Cancer gene therapy · 2026Article
- Integrative Transcriptional and Chromatin Analyses Reveal Enhancer-Mediated Regulatory Programs Driving Breast Cancer Metastasis.Molecular cancer research : MCR · 2026Article
- Telomere-driven replicative crisis is driven by large-scale changes in genomic architecture.Genome research · 2026Article
- Temporally segregated functions for Gfi1 in the development and maintenance of direction selectivity in the vertebrate retina.Current biology : CB · 2026Article
- 3D chromatin structure remodelling in cancer.Cell communication and signaling : CCS · 2026Review
- 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
- 3D chromatin architecture in cancer: mechanisms of dysregulation and emerging therapeutic strategies.Experimental & molecular medicine · 2026Review
- Tumor Microenvironmental Regulation of CAR T-Cell Therapy in High Risk Medulloblastoma.Research square · 2026Article
- Structure Variations and 3D Genome Disruption: Implications in Safety of hPSC-Based Cell Therapy.International journal of molecular sciences · 2026Review
- Hi-C for genome-wide detection of enhancer-hijacking rearrangements in routine lymphoid cancer biopsies.Cell genomics · 2026Article
- The landscape of structural variation in pediatric cancer.Cancer cell · 2026Article
- Connecting multiway enhancer-promoter interactions to changes in gene expression in cancer.bioRxiv : the preprint server for biology · 2026Article
- Redistribution of super-enhancers promotes malignancy in human hepatocellular carcinoma.Journal of advanced research · 2026Article
357 more citing papers are in PubMed but not listed here.
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Authors and funding
79 authors at 20 institutions in 9 countries.
Paul A Northcott1] Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany [2].
Catherine Lee1] Biomedical Sciences Graduate Program, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093-0685, USA [2] Tumor Initiation and Maintenance Program, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA [3].
Thomas Zichner1] European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstrasse 1, Heidelberg 69117, Germany [2].
Adrian M StützEuropean Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstrasse 1, Heidelberg 69117, Germany.
Serap Erkek1] Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany [2] European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstrasse 1, Heidelberg 69117, Germany.
Daisuke KawauchiDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
David J H ShihThe Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.
Volker HovestadtDivision of Molecular Genetics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
Marc ZapatkaDivision of Molecular Genetics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
Dominik SturmDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
David T W JonesDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
Marcel KoolDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
Marc RemkeThe Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.
Florence M G CavalliThe Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.
Scott ZuyderduynThe Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
Gary D BaderThe Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
Scott VandenBergDepartment of Pathology, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
Lourdes Adriana EsparzaTumor Initiation and Maintenance Program, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA.
Marina RyzhovaDepartment of Neuropathology, NN Burdenko Neurosurgical Institute, 4th Tverskaya-Yamskaya 16, Moscow 125047, Russia.
Wei WangDivision of Molecular Genetics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
Andrea WittmannDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
Sebastian StarkDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
Laura SieberDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
Huriye Seker-CinDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
Linda LinkeDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
Fabian KratochwilDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
Natalie JägerDivision of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
Ivo BuchhalterDivision of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
Charles D ImbuschData Management Facility, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
Gideon ZipprichData Management Facility, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
Benjamin RaederEuropean Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstrasse 1, Heidelberg 69117, Germany.
Sabine SchmidtGenomics and Proteomics Core Facility, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
Nicolle DiesslGenomics and Proteomics Core Facility, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
Stephan WolfGenomics and Proteomics Core Facility, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
Stefan WiemannGenomics and Proteomics Core Facility, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
Benedikt BrorsDivision of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
Chris LawerenzData Management Facility, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
Jürgen EilsData Management Facility, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
Hans-Jörg WarnatzDepartment of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Ihnestrasse 63-73, Berlin 14195, Germany.
Thomas RischDepartment of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Ihnestrasse 63-73, Berlin 14195, Germany.
Marie-Laure YaspoDepartment of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Ihnestrasse 63-73, Berlin 14195, Germany.
Ursula D WeberDivision of Molecular Genetics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
Cynthia C BartholomaeDivision of Translational Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 460, Heidelberg 69120, Germany.
Christof von Kalle1] Division of Translational Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 460, Heidelberg 69120, Germany [2] Heidelberg Center for Personalised Oncology (DKFZ-HIPO), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
Eszter Turányi1st Department of Pathology and Experimental Cancer Research, Semmelweis University SE, II.sz. Gyermekklinika, Budapest 1094, Hungary.
Peter Hauser2nd Department of Pediatrics, Semmelweis University, SE, II.sz. Gyermekklinika, Budapest 1094, Hungary.
Emma Sanden1] Glioma Immunotherapy Group, Division of Neurosurgery, Lund University, Paradisgatan 2, Lund 221 00, Sweden [2] Department of Clinical Sciences, Lund University, Paradisgatan 2, Lund 221 00, Sweden.
Anna Darabi1] Glioma Immunotherapy Group, Division of Neurosurgery, Lund University, Paradisgatan 2, Lund 221 00, Sweden [2] Department of Clinical Sciences, Lund University, Paradisgatan 2, Lund 221 00, Sweden.
Peter Siesjö1] Glioma Immunotherapy Group, Division of Neurosurgery, Lund University, Paradisgatan 2, Lund 221 00, Sweden [2] Department of Clinical Sciences, Lund University, Paradisgatan 2, Lund 221 00, Sweden.
Jaroslav SterbaDepartment of Pediatric Oncology, Masaryk University and University Hospital, Brno, Cernopolni 9 Brno 613 00, Czech Republic.
Karel ZitterbartDepartment of Pediatric Oncology, Masaryk University and University Hospital, Brno, Cernopolni 9 Brno 613 00, Czech Republic.
David SumerauerDepartment of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, V Úvalu 84, Prague 150 06, Czech Republic.
Peter van SluisDepartment of Oncogenomics, AMC, University of Amsterdam, Meibergdreef 9, Amsterdam 1105, AZ Netherlands.
Rogier VersteegDepartment of Oncogenomics, AMC, University of Amsterdam, Meibergdreef 9, Amsterdam 1105, AZ Netherlands.
Richard VolckmannDepartment of Oncogenomics, AMC, University of Amsterdam, Meibergdreef 9, Amsterdam 1105, AZ Netherlands.
Jan KosterDepartment of Oncogenomics, AMC, University of Amsterdam, Meibergdreef 9, Amsterdam 1105, AZ Netherlands.
Martin U SchuhmannDepartment of Neurosurgery, Tübingen University Hospital, Hoppe-Seyler Strasse 3, Tübingen 72076, Germany.
Martin EbingerDepartment of Neurosurgery, Tübingen University Hospital, Hoppe-Seyler Strasse 3, Tübingen 72076, Germany.
H Leighton GrimesDivision of Immunobiology, Program in Cancer Pathology of the Divisions of Experimental Hematology and Pathology, Program in Hematologic Malignancies of the Cancer and Blood Disease Insitute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 452229, USA.
Giles W Robinson1] Department of Developmental Neurobiology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA [2] Department of Oncology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA.
Amar GajjarDepartment of Oncology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA.
Martin MynarekDepartment of Paediatric Haematology and Oncology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg 20246, Germany.
Katja von HoffDepartment of Paediatric Haematology and Oncology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg 20246, Germany.
Stefan RutkowskiDepartment of Paediatric Haematology and Oncology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg 20246, Germany.
Torsten PietschDepartment of Neuropathology, University of Bonn, Sigmund-Freud-Str. 25, Bonn 53105, Germany.
Wolfram ScheurlenCnopf'sche Kinderklinik, Nürnberg Children's Hospital, St-Johannis-Mühlgasse 19, Nürnberg 90419, Germany.
Jörg FelsbergDepartment of Neuropathology, Heinrich-Heine-University Düsseldorf, Moorenstrasse 5, Düsseldorf 40225, Germany.
Guido ReifenbergerDepartment of Neuropathology, Heinrich-Heine-University Düsseldorf, Moorenstrasse 5, Düsseldorf 40225, Germany.
Andreas E KulozikDepartment of Pediatric Oncology, Hematology & Immunology, Heidelberg University Hospital, Im Neuenheimer Feld 430, Heidelberg 69120, Germany.
Andreas von DeimlingDepartment of Neuropathology, University of Heidelberg, Im Neuenheimer Feld 220, Heidelberg 69120, Germany.
Olaf WittDepartment of Pediatric Oncology, Hematology & Immunology, Heidelberg University Hospital, Im Neuenheimer Feld 430, Heidelberg 69120, Germany.
Roland Eils1] Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany [2] Heidelberg Center for Personalised Oncology (DKFZ-HIPO), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
Richard J Gilbertson1] Department of Developmental Neurobiology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA [2] Department of Oncology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA.
Andrey KorshunovDepartment of Neuropathology, University of Heidelberg, Im Neuenheimer Feld 220, Heidelberg 69120, Germany.
Michael D Taylor1] The Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada [2] Division of Neurosurgery, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.
Peter Lichter1] Division of Molecular Genetics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany [2] Heidelberg Center for Personalised Oncology (DKFZ-HIPO), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
Jan O Korbel1] European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstrasse 1, Heidelberg 69117, Germany [2] EMBL, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Saffron Walden CB10 1SD, UK.
Robert J Wechsler-ReyaTumor Initiation and Maintenance Program, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA.
Stefan M Pfister1] Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany [2] Department of Pediatric Oncology, Hematology & Immunology, Heidelberg University Hospital, Im Neuenheimer Feld 430, Heidelberg 69120, Germany.
Heidelberg University · DEGerman Cancer Research Center · DEUniversity of Amsterdam · NLEuropean Molecular Biology Laboratory · DELund University · SEMax Planck Institute for Molecular Genetics · DESickKids Foundation · CASt. Jude Children's Research Hospital · USUniversity Medical Center Hamburg-Eppendorf · DEHeinrich Heine University Düsseldorf · DESanford Burnham Prebys Medical Discovery Institute · USSemmelweis University · HUUniversity Children's Hospital Tübingen · DEUniversity Hospital Brno · CZUniversity Hospital Heidelberg · DEUniversity of California, San Diego · USUniversity of Toronto · CABurdenko Neurosurgery Institute · RUCincinnati Children's Hospital Medical Center · USCnopf´sche Kinderklinik · DE
Funding
Tumor Microenvironment and Cancer ImmunologyP30CA030199 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI Michael Jackson · 1985 to 2026
$107.2MThe DNA Damage Response and Tumorigenesis in the BrainP01CA096832 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI BAKER, SUZANNE J. · 2003 to 2025
$38.0MLCenter for Clinical and Translational Science and TrainingUL1TR001425 · NCATS · UNIVERSITY OF CINCINNATI · PI MEINZEN-DERR, JAREEN, STRAWN, JEFFREY ROBERT · 2015 to 2024
$37.5MTR&D 3 - Network Guided Machine LearningP41GM103504 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IDEKER, TREY · 2012 to 2024
$17.3MMouse models to discover new drivers of medulloblastomaR01CA159859 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI Michael D. Taylor, WILLIAM A WEISS · 2011 to 2026
$10.4MAn Investigation of Radial Glia as the Source of Ependymoma Stem CellsR01CA129541 · NCI · UNIVERSITY OF CAMBRIDGE · PI GILBERTSON, RICHARD · 2007 to 2016
$3.0MNCATS NIH HHS UL1 TR001425NCI NIH HHS 5P30CA030199NCI NIH HHS P01 CA096832NCI NIH HHS P30 CA030199NCI NIH HHS R01 CA129541NCI NIH HHS R01 CA159859NIGMS NIH HHS P41 GM103504NIGMS NIH HHS P41GM103504
Abstract
Medulloblastoma is a highly malignant paediatric brain tumour currently treated with a combination of surgery, radiation and chemotherapy, posing a considerable burden of toxicity to the developing child. Genomics has illuminated the extensive intertumoral heterogeneity of medulloblastoma, identifying four distinct molecular subgroups. Group 3 and group 4 subgroup medulloblastomas account for most paediatric cases; yet, oncogenic drivers for these subtypes remain largely unidentified. Here we describe a series of prevalent, highly disparate genomic structural variants, restricted to groups 3 and 4, resulting in specific and mutually exclusive activation of the growth factor independent 1 family proto-oncogenes, GFI1 and GFI1B. Somatic structural variants juxtapose GFI1 or GFI1B coding sequences proximal to active enhancer elements, including super-enhancers, instigating oncogenic activity. Our results, supported by evidence from mouse models, identify GFI1 and GFI1B as prominent medulloblastoma oncogenes and implicate 'enhancer hijacking' as an efficient mechanism driving oncogene activation in a childhood cancer.
Indexed as
AnimalsChildChromosomes, Human, Pair 9DNA-Binding ProteinsEnhancer Elements, GeneticGenomic Structural VariationHumansMedulloblastomaMiceOncogenesProto-Oncogene ProteinsRepressor ProteinsTranscription FactorsDNA-Binding ProteinsGFI1B protein, humanGFI1 protein, humanProto-Oncogene ProteinsRepressor ProteinsTranscription Factors
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