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

  • Laboratory Investigation - Human/Animal Tissue
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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.

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Acknowledgments

This study was supported by grant IGA MZCR NR9125-4/2006. We thank Dr Michal Kyr for his technical help with statistical analysis.

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Authors and Affiliations

  1. Department of Pediatric Oncology, University Hospital Brno, Masaryk University, Cernopolni 9, 613 00, Brno, Czech Republic

    Karel Zitterbart, Dagmar Kantorova, Zdenek Pavelka, Renata Veselska & Jaroslav Sterba

  2. Department of Medical Genetics, University Hospital Brno, Brno, Czech Republic

    Hana Filkova, Lenka Tomasikova, Eva Necesalova, Iva Slamova, Vladimira Vranova, Dita Zezulkova, Martina Pesakova & Petr Kuglik

  3. Department of Experimental Biology, School of Science, Masaryk University, Brno, Czech Republic

    Hana Filkova, Eva Necesalova, Iva Slamova, Vladimira Vranova, Dita Zezulkova, Martina Pesakova, Renata Veselska & Petr Kuglik

  4. Department of Pathological Anatomy, St. Anne’s University Hospital, Masaryk University, Brno, Czech Republic

    Iva Zambo

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  1. Karel Zitterbart
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Zitterbart, K., Filkova, H., Tomasikova, L. et al. Low-level copy number changes of MYC genes have a prognostic impact in medulloblastoma. J Neurooncol 102, 25–33 (2011). https://doi.org/10.1007/s11060-010-0289-3

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