Subgroup-specific structural variation across 1,000 medulloblastoma genomes View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-08

AUTHORS

Paul A. Northcott, David J. H. Shih, John Peacock, Livia Garzia, A. Sorana Morrissy, Thomas Zichner, Adrian M. Stütz, Andrey Korshunov, Jüri Reimand, Steven E. Schumacher, Rameen Beroukhim, David W. Ellison, Christian R. Marshall, Anath C. Lionel, Stephen Mack, Adrian Dubuc, Yuan Yao, Vijay Ramaswamy, Betty Luu, Adi Rolider, Florence M. G. Cavalli, Xin Wang, Marc Remke, Xiaochong Wu, Readman Y. B. Chiu, Andy Chu, Eric Chuah, Richard D. Corbett, Gemma R. Hoad, Shaun D. Jackman, Yisu Li, Allan Lo, Karen L. Mungall, Ka Ming Nip, Jenny Q. Qian, Anthony G. J. Raymond, Nina Thiessen, Richard J. Varhol, Inanc Birol, Richard A. Moore, Andrew J. Mungall, Robert Holt, Daisuke Kawauchi, Martine F. Roussel, Marcel Kool, David T. W. Jones, Hendrick Witt, Africa Fernandez-L, Anna M. Kenney, Robert J. Wechsler-Reya, Peter Dirks, Tzvi Aviv, Wieslawa A. Grajkowska, Marta Perek-Polnik, Christine C. Haberler, Olivier Delattre, Stéphanie S. Reynaud, François F. Doz, Sarah S. Pernet-Fattet, Byung-Kyu Cho, Seung-Ki Kim, Kyu-Chang Wang, Wolfram Scheurlen, Charles G. Eberhart, Michelle Fèvre-Montange, Anne Jouvet, Ian F. Pollack, Xing Fan, Karin M. Muraszko, G. Yancey Gillespie, Concezio Di Rocco, Luca Massimi, Erna M. C. Michiels, Nanne K. Kloosterhof, Pim J. French, Johan M. Kros, James M. Olson, Richard G. Ellenbogen, Karel Zitterbart, Leos Kren, Reid C. Thompson, Michael K. Cooper, Boleslaw Lach, Roger E. McLendon, Darell D. Bigner, Adam Fontebasso, Steffen Albrecht, Nada Jabado, Janet C. Lindsey, Simon Bailey, Nalin Gupta, William A. Weiss, László Bognár, Almos Klekner, Timothy E. Van Meter, Toshihiro Kumabe, Teiji Tominaga, Samer K. Elbabaa, Jeffrey R. Leonard, Joshua B. Rubin, Linda M. Liau, Erwin G. Van Meir, Maryam Fouladi, Hideo Nakamura, Giuseppe Cinalli, Miklós Garami, Peter Hauser, Ali G. Saad, Achille Iolascon, Shin Jung, Carlos G. Carlotti, Rajeev Vibhakar, Young Shin Ra, Shenandoah Robinson, Massimo Zollo, Claudia C. Faria, Jennifer A. Chan, Michael L. Levy, Poul H. B. Sorensen, Matthew Meyerson, Scott L. Pomeroy, Yoon-Jae Cho, Gary D. Bader, Uri Tabori, Cynthia E. Hawkins, Eric Bouffet, Stephen W. Scherer, James T. Rutka, David Malkin, Steven C. Clifford, Steven J. M. Jones, Jan O. Korbel, Stefan M. Pfister, Marco A. Marra, Michael D. Taylor

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. More... »

PAGES

49

Journal

TITLE

Nature

ISSUE

7409

VOLUME

488

Author Affiliations

  • German Cancer Research Center
  • University of Toronto
  • Hospital for Sick Children
  • European Molecular Biology Laboratory
  • Dana–Farber Cancer Institute
  • St. Jude Children's Research Hospital
  • BC Cancer Agency
  • University Hospital Heidelberg
  • Memorial Sloan Kettering Cancer Center
  • Vanderbilt University Medical Center
  • Sanford Burnham Prebys Medical Discovery Institute
  • Children's Memorial Health Institute
  • Medical University of Vienna
  • Institute Curie
  • University Hospital of Lausanne
  • Seoul National University Children's Hospital
  • Johns Hopkins University
  • University of Lyon System
  • Claude Bernard University Lyon 1
  • University of Pittsburgh
  • University of Michigan–Ann Arbor
  • University of Alabama at Birmingham
  • Catholic University of the Sacred Heart
  • Erasmus University Medical Center
  • Seattle Children's Hospital
  • University Hospital Brno
  • Hamilton General Hospital
  • Duke University
  • McGill University
  • Montreal Children's Hospital
  • Newcastle University
  • University of California, San Francisco
  • University of Debrecen
  • Virginia Commonwealth University
  • Tohoku University
  • Saint Louis University
  • Washington University in St. Louis
  • University of California Los Angeles
  • Emory University
  • Kumamoto University
  • Semmelweis University
  • University of Arkansas for Medical Sciences
  • University of Naples Federico II
  • University of Sao Paulo
  • University of Colorado Anschutz Medical Campus
  • Asan Medical Center
  • Case Western Reserve University
  • University of Calgary
  • Rady Children's Hospital-San Diego
  • Stanford University
  • University of British Columbia
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature11327

    DOI

    http://dx.doi.org/10.1038/nature11327

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1039022488

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/22832581


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