Journal of Neuro-Oncology

, Volume 102, Issue 1, pp 25–33

Low-level copy number changes of MYC genes have a prognostic impact in medulloblastoma

Authors

    • Department of Pediatric OncologyUniversity Hospital Brno, Masaryk University
  • Hana Filkova
    • Department of Medical GeneticsUniversity Hospital Brno
    • Department of Experimental Biology, School of ScienceMasaryk University
  • Lenka Tomasikova
    • Department of Medical GeneticsUniversity Hospital Brno
  • Eva Necesalova
    • Department of Medical GeneticsUniversity Hospital Brno
    • Department of Experimental Biology, School of ScienceMasaryk University
  • Iva Zambo
    • Department of Pathological AnatomySt. Anne’s University Hospital, Masaryk University
  • Dagmar Kantorova
    • Department of Pediatric OncologyUniversity Hospital Brno, Masaryk University
  • Iva Slamova
    • Department of Medical GeneticsUniversity Hospital Brno
    • Department of Experimental Biology, School of ScienceMasaryk University
  • Vladimira Vranova
    • Department of Medical GeneticsUniversity Hospital Brno
    • Department of Experimental Biology, School of ScienceMasaryk University
  • Dita Zezulkova
    • Department of Medical GeneticsUniversity Hospital Brno
    • Department of Experimental Biology, School of ScienceMasaryk University
  • Martina Pesakova
    • Department of Medical GeneticsUniversity Hospital Brno
    • Department of Experimental Biology, School of ScienceMasaryk University
  • Zdenek Pavelka
    • Department of Pediatric OncologyUniversity Hospital Brno, Masaryk University
  • Renata Veselska
    • Department of Pediatric OncologyUniversity Hospital Brno, Masaryk University
    • Department of Experimental Biology, School of ScienceMasaryk University
  • Petr Kuglik
    • Department of Medical GeneticsUniversity Hospital Brno
    • Department of Experimental Biology, School of ScienceMasaryk University
  • Jaroslav Sterba
    • Department of Pediatric OncologyUniversity Hospital Brno, Masaryk University
Laboratory Investigation - Human/Animal Tissue

DOI: 10.1007/s11060-010-0289-3

Cite this article as:
Zitterbart, K., Filkova, H., Tomasikova, L. et al. J Neurooncol (2011) 102: 25. doi:10.1007/s11060-010-0289-3
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Abstract

High-level amplifications of MYC genes are associated with poor outcomes in childhood medulloblastoma (MB). However, the occurrence of MYCN and MYCC copy number increases below the intense amplification pattern is rarely reported, and its clinical impact has not yet been determined. Here, we describe this phenomenon and its prognostic significance in a cohort of 29 MB patients. Using interphase fluorescence in situ hybridization (I-FISH), low-level copy number alterations, i.e. gain of MYCN, were shown in 5/27 (19%) samples, whereas amplification was revealed in only 1/27 (4%) samples. MYCC gain was revealed in 6/29 (21%) MB, while amplification was disclosed in only 2/29 (7%). Hyperploidy and co-incidence of gains in both MYC loci were frequently observed in samples with copy number aberrations. Survival analysis has clearly shown that MYC copy number increases are associated with lowered event-free survival and overall survival in MB. In the case of MYCN, this negative correlation was statistically significant. We conclude that limited numerical alterations in loci 2p24 (MYCN) and 8q24 (MYCC), as assessed by I-FISH, are present in MB with a higher frequency than high-level amplifications. Poor prognoses were observed in patients with copy number increases in MYC genes. Our data illustrate the importance of further investigations in multicenter trials to better refine the emerging genomic-based prognostic stratification in MB.

Keywords

MedulloblastomaAmplificationGainMYCNMYCCI-FISH

Copyright information

© Springer Science+Business Media, LLC. 2010