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

  • Karel Zitterbart
  • Hana Filkova
  • Lenka Tomasikova
  • Eva Necesalova
  • Iva Zambo
  • Dagmar Kantorova
  • Iva Slamova
  • Vladimira Vranova
  • Dita Zezulkova
  • Martina Pesakova
  • Zdenek Pavelka
  • Renata Veselska
  • Petr Kuglik
  • Jaroslav Sterba
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

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

Authors and Affiliations

  • Karel Zitterbart
    • 1
  • Hana Filkova
    • 2
    • 3
  • Lenka Tomasikova
    • 2
  • Eva Necesalova
    • 2
    • 3
  • Iva Zambo
    • 4
  • Dagmar Kantorova
    • 1
  • Iva Slamova
    • 2
    • 3
  • Vladimira Vranova
    • 2
    • 3
  • Dita Zezulkova
    • 2
    • 3
  • Martina Pesakova
    • 2
    • 3
  • Zdenek Pavelka
    • 1
  • Renata Veselska
    • 1
    • 3
  • Petr Kuglik
    • 2
    • 3
  • Jaroslav Sterba
    • 1
  1. 1.Department of Pediatric OncologyUniversity Hospital Brno, Masaryk UniversityBrnoCzech Republic
  2. 2.Department of Medical GeneticsUniversity Hospital BrnoBrnoCzech Republic
  3. 3.Department of Experimental Biology, School of ScienceMasaryk UniversityBrnoCzech Republic
  4. 4.Department of Pathological AnatomySt. Anne’s University Hospital, Masaryk UniversityBrnoCzech Republic