gms | German Medical Science

57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

German Society for Neuropathology and Neuroanatomy

12. - 15.09.2012, Erlangen

57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

Article

Send article

MYCN-amplified medulloblastomas: biological and clinical heterogeneity

Meeting Abstract

Search Medline for

  • presenting/speaker Andrey Korshunov - University of Heidelberg, Department of Neuropathology and Department of Pediatric Oncology, Heidelberg, Germany; German Cancer Research Center, Clinical Cooperation Unit Neuropathology, Division Molecular Genetics, and Division Biostatistics, Heidelberg, Germany
  • M. Remke - University of Heidelberg, Department of Neuropathology and Department of Pediatric Oncology, Heidelberg, Germany; German Cancer Research Center, Clinical Cooperation Unit Neuropathology, Division Molecular Genetics, and Division Biostatistics, Heidelberg, Germany
  • M. Kool - University of Heidelberg, Department of Neuropathology and Department of Pediatric Oncology, Heidelberg, Germany; German Cancer Research Center, Clinical Cooperation Unit Neuropathology, Division Molecular Genetics, and Division Biostatistics, Heidelberg, Germany
  • T. Hielscher - University of Heidelberg, Department of Neuropathology and Department of Pediatric Oncology, Heidelberg, Germany; German Cancer Research Center, Clinical Cooperation Unit Neuropathology, Division Molecular Genetics, and Division Biostatistics, Heidelberg, Germany
  • P.A. Northcott - University of Heidelberg, Department of Neuropathology and Department of Pediatric Oncology, Heidelberg, Germany; German Cancer Research Center, Clinical Cooperation Unit Neuropathology, Division Molecular Genetics, and Division Biostatistics, Heidelberg, Germany
  • H. Wit - University of Heidelberg, Department of Neuropathology and Department of Pediatric Oncology, Heidelberg, Germany; German Cancer Research Center, Clinical Cooperation Unit Neuropathology, Division Molecular Genetics, and Division Biostatistics, Heidelberg, Germany
  • D.T.W. Jones - University of Heidelberg, Department of Neuropathology and Department of Pediatric Oncology, Heidelberg, Germany; German Cancer Research Center, Clinical Cooperation Unit Neuropathology, Division Molecular Genetics, and Division Biostatistics, Heidelberg, Germany
  • M. Ryzhova - University of Heidelberg, Department of Neuropathology and Department of Pediatric Oncology, Heidelberg, Germany; German Cancer Research Center, Clinical Cooperation Unit Neuropathology, Division Molecular Genetics, and Division Biostatistics, Heidelberg, Germany
  • A. Benner - University of Heidelberg, Department of Neuropathology and Department of Pediatric Oncology, Heidelberg, Germany; German Cancer Research Center, Clinical Cooperation Unit Neuropathology, Division Molecular Genetics, and Division Biostatistics, Heidelberg, Germany
  • P. Lichter - University of Heidelberg, Department of Neuropathology and Department of Pediatric Oncology, Heidelberg, Germany; German Cancer Research Center, Clinical Cooperation Unit Neuropathology, Division Molecular Genetics, and Division Biostatistics, Heidelberg, Germany
  • A. von Deimling - University of Heidelberg, Department of Neuropathology and Department of Pediatric Oncology, Heidelberg, Germany; German Cancer Research Center, Clinical Cooperation Unit Neuropathology, Division Molecular Genetics, and Division Biostatistics, Heidelberg, Germany
  • S. M. Pfister - University of Heidelberg, Department of Neuropathology and Department of Pediatric Oncology, Heidelberg, Germany; German Cancer Research Center, Clinical Cooperation Unit Neuropathology, Division Molecular Genetics, and Division Biostatistics, Heidelberg, Germany

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie. 57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN). Erlangen, 12.-15.09.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. Doc12dgnnPP5.5

doi: 10.3205/12dgnn105, urn:nbn:de:0183-12dgnn1054

Published: September 11, 2012

© 2012 Korshunov et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

Text

Amplifications of MYC define a subset of high-risk medulloblastoma patients. However, the prognostic role of MYCN oncogene amplification remains unresolved. We aimed to evaluate the prognostic value of this alteration in 67 medulloblastomas with MYCN amplification (MYCN-MB). Twenty-one tumors were examined using gene expression profiling and array-CGH, whereas for 46 MYCN-MB immunohistochemical analysis and FISH were performed.

Considerable heterogeneity within MYCN-MB in terms of genetics, tumor biology, and clinical outcome was found. Transcriptomic analysis revealed SHH-driven tumorigenesis in a subset of MYCN-MBs indicating a biological dichotomy of MYCN-MB. Activation of SHH was accompanied by variant-specific cytogenetic aberrations including deletion of 9q. Non-SHH MYCN-MB were associated with gain of 7q and isochromosome 17q. Among clinically relevant variables, SHH signature (detected by expression profiling and/or immunohistochemistry) and 10q loss for non-SHH tumors comprised the most powerful markers of favorable prognosis in MYCN-MB.

Thus assessment of molecular signature and 10q copy-number status may improve risk stratification and delineate MYCN-MB with the same dismal prognosis as MYC amplified tumors. Furthermore, based on the enrichment of MYCN and GLI2 co-amplifications in SHH-driven medulloblastoma, high-level gains of these downstream signaling intermediates should be taken into account before a patient is enrolled into a clinical trial using SMO inhibitors.