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Failure of human rhombic lip differentiation underlies medulloblastoma formation
LD. Hendrikse, P. Haldipur, O. Saulnier, J. Millman, AH. Sjoboen, AW. Erickson, W. Ong, V. Gordon, L. Coudière-Morrison, AL. Mercier, M. Shokouhian, RA. Suárez, M. Ly, S. Borlase, DS. Scott, MC. Vladoiu, H. Farooq, O. Sirbu, T. Nakashima, S....
Language English Country England, Great Britain
Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
Grant support
R01 NS095733
NINDS NIH HHS - United States
R21 NS117848
NINDS NIH HHS - United States
R37 NS095733
NINDS NIH HHS - United States
R01 CA255369
NCI NIH HHS - United States
R01 NS080390
NINDS NIH HHS - United States
R01 NS106155
NINDS NIH HHS - United States
R01 CA159859
NCI NIH HHS - United States
NLK
Nature Journals Online
from 1997
Nature Journal Archive
from 1997
ProQuest Central
from 1990-01-04 to 1 year ago
Nursing & Allied Health Database (ProQuest)
from 1990-01-04 to 1 year ago
Health & Medicine (ProQuest)
from 1990-01-04 to 1 year ago
Psychology Database (ProQuest)
from 1990-01-04 to 1 year ago
Public Health Database (ProQuest)
from 1990-01-04 to 1 year ago
- MeSH
- Ki-67 Antigen metabolism MeSH
- Cell Differentiation * genetics MeSH
- Cell Lineage MeSH
- Histone Demethylases MeSH
- Humans MeSH
- Medulloblastoma * classification genetics pathology MeSH
- Metencephalon * embryology pathology MeSH
- Cerebellum embryology pathology MeSH
- Mutation MeSH
- Cerebellar Neoplasms * classification genetics pathology MeSH
- Hedgehog Proteins metabolism MeSH
- T-Box Domain Proteins metabolism MeSH
- Repressor Proteins MeSH
- Muscle Proteins MeSH
- Otx Transcription Factors deficiency genetics MeSH
- Core Binding Factor alpha Subunits genetics MeSH
- Transcription Factors MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
Medulloblastoma (MB) comprises a group of heterogeneous paediatric embryonal neoplasms of the hindbrain with strong links to early development of the hindbrain1-4. Mutations that activate Sonic hedgehog signalling lead to Sonic hedgehog MB in the upper rhombic lip (RL) granule cell lineage5-8. By contrast, mutations that activate WNT signalling lead to WNT MB in the lower RL9,10. However, little is known about the more commonly occurring group 4 (G4) MB, which is thought to arise in the unipolar brush cell lineage3,4. Here we demonstrate that somatic mutations that cause G4 MB converge on the core binding factor alpha (CBFA) complex and mutually exclusive alterations that affect CBFA2T2, CBFA2T3, PRDM6, UTX and OTX2. CBFA2T2 is expressed early in the progenitor cells of the cerebellar RL subventricular zone in Homo sapiens, and G4 MB transcriptionally resembles these progenitors but are stalled in developmental time. Knockdown of OTX2 in model systems relieves this differentiation blockade, which allows MB cells to spontaneously proceed along normal developmental differentiation trajectories. The specific nature of the split human RL, which is destined to generate most of the neurons in the human brain, and its high level of susceptible EOMES+KI67+ unipolar brush cell progenitor cells probably predisposes our species to the development of G4 MB.
2nd Department of Pediatrics Semmelweis University Budapest Hungary
Adaptive Oncology Ontario Institute for Cancer Research Toronto Ontario Canada
Alberta Children's Hospital Research Institute Calgary Alberta Canada
Assistance Publique Hôpitaux de Paris Hôpital Necker Enfants Malades Paris France
Brotman Baty Institute for Precision Medicine Seattle WA USA
Canada's Michael Smith Genome Sciences Centre BC Cancer Agency Vancouver British Columbia Canada
Cancer Research Program McGill University Health Centre Research Institute Montreal Quebec Canada
CancerCare Manitoba Research Institute Winnipeg Manitoba Canada
CBIO Centre for Computational Biology PSL Research University MINES ParisTech Paris France
CEINGE Biotecnologie Avanzate Naples Italy
Center for Integrative Brain Research Seattle Children's Research Institute Seattle WA USA
Centre de Pathologie EST Groupement Hospitalier EST Université de Lyon Bron France
Charbonneau Cancer Institute University of Calgary Calgary Alberta Canada
Clinical Research Division Fred Hutchinson Cancer Research Center Seattle WA USA
Computational Biology Program Ontario Institute for Cancer Research Toronto Ontario Canada
Department of Anatomical and Cellular Pathology The Chinese University of Hong Kong Shatin Hong Kong
Department of Biochemistry and Medical Genetics University of Manitoba Winnipeg Manitoba Canada
Department of Human Genetics McGill University Montreal Quebec Canada
Department of Laboratory Medicine and Pathobiology University of Toronto Toronto Ontario Canada
Department of Laboratory Medicine and Pathology Mayo Clinic Rochester MN USA
Department of Medical Biophysics University of Toronto Toronto Ontario Canada
Department of Medical Genetics University of British Columbia Vancouver British Columbia Canada
Department of Molecular Genetics University of Toronto Toronto Ontario Canada
Department of Molecular Oncology BC Cancer Agency Vancouver British Columbia Canada
Department of Neurological Surgery University of California San Francisco San Francisco CA USA
Department of Neurological Surgery University of Pittsburgh School of Medicine Pittsburgh PA USA
Department of Neurological Surgery Vanderbilt Medical Center Nashville TN USA
Department of Neurology Erasmus University Medical Center Rotterdam Netherlands
Department of Neurology University of California San Francisco San Francisco CA USA
Department of Neurology Vanderbilt Medical Center Nashville TN USA
Department of Neurosurgery Duke University Durham NC USA
Department of Neurosurgery Hospital Infantil de Mexico Federico Gomez Mexico City Mexico
Department of Neurosurgery Kitasato University School of Medicine Sagamihara Japan
Department of Neurosurgery University of Alabama at Birmingham Birmingham AL USA
Department of Neurosurgery University of Ulsan Asan Medical Center Seoul South Korea
Department of Pathology and Laboratory Medicine Hamilton General Hospital Hamilton Ontario Canada
Department of Pathology Cedars Sinai Medical Center Los Angeles CA USA
Department of Pathology Duke University Durham NC USA
Department of Pathology Erasmus University Medical Center Rotterdam Netherlands
Department of Pathology St Jude Children's Research Hospital Memphis TN USA
Department of Pathology The Children's Memorial Health Institute Warsaw Poland
Department of Pathology University of California San Francisco San Francisco CA USA
Department of Pediatric Neurosurgery Santobono Pausilipon Children's Hospital Naples Italy
Department of Pediatric Oncology Masaryk University School of Medicine Brno Czech Republic
Department of Pediatrics Hematology and Oncology Case Western Reserve Cleveland OH USA
Department of Pediatrics University of California San Francisco San Francisco CA USA
Department of Pediatrics University of Colorado Denver Aurora CO USA
Department of Surgery The Chinese University of Hong Kong Shatin Hong Kong
Department of Tumor Cell Biology St Jude Children's Research Hospital Memphis TN USA
Departments of Neuroscience Washington University School of Medicine in St Louis St Louis MO USA
Departments of Pediatrics and Human Genetics McGill University Montreal Quebec Canada
Developmental and Stem Cell Biology Program The Hospital for Sick Children Toronto Ontario Canada
Division of Brain Tumor Translational Research National Cancer Center Research Institute Tokyo Japan
Division of Neurosurgery Centro Hospitalar Lisboa Norte Hospital de Santa Maria Lisbon Portugal
Division of Neurosurgery The Hospital for Sick Children Toronto Ontario Canada
Division of Pediatric Hematology Oncology Mayo Clinic Rochester MN USA
Division of Pediatric Neurooncology German Cancer Research Center Heidelberg Germany
Division of Pediatric Neurosurgery Case Western Reserve Cleveland OH USA
Division of Stem Cell Research Institute for Clinical Research Osaka National Hospital Osaka Japan
Fondazione IRCCS Istituto Nazionale Tumori Milan Italy
INSERM U1028 CNRS UMR5292 Centre de Recherche en Neurosciences Université de Lyon Lyon France
INSERM U830 Institut Curie Paris France
INSERM U900 Institut Curie Paris France
Instituto Nacional De Pediatría de México Mexico City Mexico
Lady Davis Research Institute Jewish General Hospital Montreal Quebec Canada
McGill University Genome Centre McGill University Montreal Quebec Canada
Pediatrics Virginia Commonwealthy University School of Medicine Richmond VA USA
Princess Margaret Cancer Centre University Health Network Toronto Ontario Canada
PSL Research University Institut Curie Paris France
SIREDO Oncology Center Institut Curie Paris France
Surgical Pathology Unit San Camillo Forlanini Hospital Rome Italy
The Research Institute of the McGill University Health Center Montreal Quebec Canada
U O Neurochirurgia Istituto Giannina Gaslini Genova Italy
Unit of Somatic Genetics Institut Curie Paris France
References provided by Crossref.org
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- 700 1_
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- 700 1_
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- 700 1_
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