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Acta Neuropathol (2012) 123:515527 DOI 10.1007/s00401-011-0918-8
ORIGINAL PAPER
Biological and clinical heterogeneity of MYCN-amplied medulloblastoma
Andrey Korshunov Marc Remke Marcel Kool Thomas Hielscher Paul A. Northcott
Dan Williamson Elke Pfaff Hendrik Witt David T. W. Jones Marina Ryzhova
Yoon-Jae Cho Andrea Wittmann Axel Benner William A. Weiss Andreas von Deimling
Wolfram Scheurlen Andreas E. Kulozik Steven C. Clifford V. Peter Collins
Frank Westermann Michael D. Taylor Peter Lichter Stefan M. Pster
Received: 7 October 2011 / Revised: 9 November 2011 / Accepted: 13 November 2011 / Published online: 9 December 2011 Springer-Verlag 2011
Abstract Focal high-level amplications of MYC (or MYCC) dene a subset of high-risk medulloblastoma patients. However, the prognostic role of MYCN oncogene amplication remains unresolved. We aimed to evaluate the prognostic value of this alteration alone and in combination with biological modiers in 67 pediatric
medulloblastomas with MYCN amplication (MYCN-MB). Twenty-one MYCN-MB were examined using gene expression proling and array-CGH, whereas for 46 tumors immunohistochemical analysis and FISH were performed. All 67 tumors were further subjected to mutational analyses. We compared molecular, clinical, and prognostic characteristics both within biological MYCN-MB groups and with non-amplied tumors. Transcriptomic analysis revealed SHH-driven tumorigenesis in a subset of MYCN-
Electronic supplementary material The online version of this article (doi:http://dx.doi.org/10.1007/s00401-011-0918-8
Web End =10.1007/s00401-011-0918-8 ) contains supplementary material, which is available to authorized users.
A. Korshunov A. von Deimling
Department of Neuropathology, University of Heidelberg, Heidelberg, Germany
A. Korshunov A. von Deimling
Clinical Cooperation Unit Neuropathology, German Cancer Research Center, Heidelberg, Germany
M. Remke M. Kool E. Pfaff H. Witt
D. T. W. Jones A. Wittmann P. Lichter S. M. Pster
Division Molecular Genetics, German Cancer Research Center, Heidelberg, Germany
M. Remke H. Witt A. E. Kulozik S. M. Pster
Department of Pediatric Oncology, Hematologyand Immunology, University of Heidelberg, Heidelberg, Germany
T. Hielscher A. Benner
Division Biostatistics, German Cancer Research Center, Heidelberg, Germany
P. A. Northcott M. D. Taylor
Program in Developmental and Stem Cell Biology, Division of Neurosurgery, Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, University of Toronto, Toronto, Canada
D. Williamson S. C. Clifford
Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK
M. Ryzhova
NN Burdenko Neurosurgical Institute, Moscow, Russia
Y.-J. ChoChildrens Hospital Boston, Boston, USA
W. A....