Publication

Subgroup specific structural variation across 1,000 medulloblastoma genomes

Downloadable Content

Persistent URL
Last modified
  • 05/15/2025
Type of Material
Authors
    Paul A. Northcott, Hospital for Sick ChildrenDavid J. H. Shih, Hospital for Sick ChildrenJohn Peacock, Hospital for Sick ChildrenLivia Garzia, Hospital for Sick ChildrenSorana Morrissy, Hospital for Sick ChildrenThomas Zichner, European Molecular Biology LaboratoryAdrian Stuetz, European Molecular Biology LaboratoryAndrey Korshunov, German Cancer Research CenterJuri Reimand, University of TorontoSteven E. Schumacher, Dana-Farber Cancer InstituteRameen Beroukhim, Dana-Farber Cancer InstituteDavid W. Ellison, St Jude Children's Research HospitalChristian Marshall, University of TorontoAnath C. Lionel, Hospital for Sick ChildrenStephen Mack, Hospital for Sick ChildrenAdrian Dubuc, Hospital for Sick ChildrenYuan Yao, Hospital for Sick ChildrenVijay Ramaswamy, Hospital for Sick ChildrenBetty Luu, Hospital for Sick ChildrenAdi Rolider, Hospital for Sick ChildrenFlorence Cavalli, Hospital for Sick ChildrenXin Wang, Hospital for Sick ChildrenMarc Remke, Hospital for Sick ChildrenXiaochong Wu, Hospital for Sick ChildrenReadman Y. B. Chiu, Michael Smith Genome Sciences CentreAndy Chu, Michael Smith Genome Sciences CentreEric Chuah, Michael Smith Genome Sciences CentreRichard D. Corbett, Michael Smith Genome Sciences CentreGeema R. Hoad, Michael Smith Genome Sciences CentreShaun D. Jackman, Michael Smith Genome Sciences CentreYisu Li, Michael Smith Genome Sciences CentreAllan Lo, Michael Smith Genome Sciences CentreKaren Mungall, Michael Smith Genome Sciences CentreKa Ming Nip, Michael Smith Genome Sciences CentreJenny Q. Qian, Michael Smith Genome Sciences CentreAnthony G. J. Raymond, Michael Smith Genome Sciences CentreNina Thiessen, Michael Smith Genome Sciences CentreRichard J. Varhol, Michael Smith Genome Sciences CentreInanc Birol, Michael Smith Genome Sciences CentreRichard A. Moore, Michael Smith Genome Sciences CentreAndrew J. Mungall, Michael Smith Genome Sciences CentreRobert Holt, Michael Smith Genome Sciences CentreDaisuke Kawauchi, St Jude Children's Research HospitalMartine F. Roussel, St Jude Children's Research HospitalMarcel Kool, German Cancer Research CenterDavid T. W. Jones, German Cancer Research CenterHendrick Witt, University Hospital HeidelbergAfrica Fernandez-L, Memorial Sloan-Kettering Cancer CenterAnna M. Kenney, Emory UniversityRobert J. Wechsler-Reya, Sanford-Burnham Medical Research InstitutePeter Dirks, Hospital for Sick ChildrenTzvi Aviv, Hospital for Sick ChildrenWieslawa A. Grajkowska, The Children's Memorial Health InstituteMarta Perek-Polnik, The Children's Memorial Health InstituteChristine C. Haberler, Medical University of ViennaOlivier Delattre, Institut CurieStephanie S Reynaud, Institut CurieFrancois F. Doz, Institut CurieSarah S. Pernet-Fattet, CHUV University HospitalByung Kyu Cho, Seoul National University Children's HospitalSeung Ki Kim, Seoul National University Children's HospitalKyu Chang Wang, Seoul National University Children's HospitalWolfram Scheurlen, Cnopf´sche KinderklinikCharles G. Eberhart, Johns Hopkins UniversityMichelle Fevre-Montange, Université de LyonAnne Jouvet, Université de LyonIan F. Pollack, University of PittsburghXing Fan, University of MichiganKarian M. Muraszko, University of MichiganG. Yancey Gillespie, University of Alabama BirminghamConcezio Di Rocco, Catholic University Medical SchoolLuca Massimi, Catholic University Medical SchoolErna M. C. Michiels, Erasmus MCNanne K. Kloosterhof, Erasmus MCPim J French, Erasmus MCJohan M. Kros, Erasmus MCJames M. Olson, Fred Hutchinson Cancer Research CenterRichard G. Ellenbogen, University of WashingtonKarel Zitterbart, Masaryk UniversityLeos Kren, University Hospital BrnoReid C. Thompson, Vanderbilt Medical CenterMichael K. Cooper, Vanderbilt Medical CenterBoleslaw Lach, McMaster UniversityRoger E. McLendon, Duke UniversityDarell D. Bigner, Duke UniversityAdam Fontebasso, McGill UniversitySteffen Albrecht, McGill UniversityNada Jabado, McGill UniversityJanet C. Lindsey, Newcastle UniversitySimon Bailey, Newcastle UniversityNalin Gupta, University of California San FranciscoWilliam A. Weiss, University of California at San FranciscoLaszlo Bognar, University of DebrecenAlmos Klekner, University of DebrecenTimothy E. Van Meter, Virginia Commonwealthy UniversityToshihiro Kumabe, Tohoku UniversityTeiji Tominaga, Tohoku UniversitySamer K Elbabaa, Saint Louis University School of MedicineJeffrey R. Leonard, Washington University School of MedicineJoshua B. Rubin, Washington University School of MedicineLinda B. Liau, David Geffen School of Medicine at UCLAErwin Van Meir, Emory University
Language
  • English
Date
  • 2012-08-02
Publisher
  • Nature Publishing Group
Publication Version
Copyright Statement
  • © 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
Final Published Version (URL)
Title of Journal or Parent Work
ISSN
  • 0028-0836
Volume
  • 488
Issue
  • 7409
Start Page
  • 49
End Page
  • 56
Grant/Funding Information
  • JK and SP were supported by a grant from the German Cancer Aid (109252).
  • Canada's Michael Smith Genome Sciences Centre is supported by the BC Cancer Foundation.
  • PAN was supported by a Restracomp Fellowship (Hospital for Sick Children) and is currently a Roman-Herzog Postdoctoral Fellow (Hertie Foundation).
  • Salary support for LG was provided by the Ontario Institute for Cancer Research through funding provided by the Government of Ontario.
  • JR is supported by The Children's Discovery Institute.
  • Funding is acknowledged from the Pediatric Brain Tumour Foundation (MDT and JTR), and the National Institutes of Health (CA159859 to MDT, RWR, and BW), Genome Canada, Genome BC, Terry Fox Research Institute, Ontario Institute for Cancer Research, Pediatric Oncology Group Ontario, Funds from ‘The Family of Kathleen Lorette’ and the Clark H. Smith Brain Tumour Centre, Montreal Children’s Hospital Foundation, Hospital for Sick Children: Sonia and Arthur Labatt Brain Tumour Research Centre, Chief of Research Fund, Cancer Genetics Program, Garron Family Cancer Centre, B.R.A.I.N. Child, CIHR (grant # ATE-110814); the University of Toronto McLaughlin Centre, CIHR Institute of Cancer Research (grant # AT1 – 112286) and C17 through the Advancing Technology Innovation through Discovery competition (Project Title: The Canadian Pediatric Cancer Genome Consortium: Translating next-generation sequencing technologies into improved therapies for high-risk childhood cancer).
  • MDT is the recipient of a CIHR Clinician-Scientist Phase II award, and was formerly a Sontag Distinguished Scholar with funds from the Sontag Foundation.
Supplemental Material (URL)
Abstract
  • Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4α. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-β signalling in Group 3, and NF-κB signalling in Group 4, suggest future avenues for rational, targeted therapy. © 2012 Macmillan Publishers Limited. All rights reserved.
Author Notes
Keywords
Research Categories
  • Health Sciences, Oncology
  • Health Sciences, Medicine and Surgery
  • Biology, Neuroscience
  • Biology, General

Tools

Relations

In Collection:

Items

Thumbnail Title File Description Date Uploaded Visibility Actions
file details Publication File - s9cm1.pdf Primary Content 2025-03-15 Public Download