title: Low-level copy number changes of MYC genes have a prognostic impact in medulloblastoma.
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.
authors.affiliation: Department of Pediatric Oncology, University Hospital Brno, Masaryk University, Cernopolni 9, 613 00 Brno, Czech Republic. kzitter@med.muni.cz
authors.forename: Karel
authors.initials: K
authors.lastname: Zitterbart
authors.forename: Hana
authors.initials: H
authors.lastname: Filkova
authors.forename: Lenka
authors.initials: L
authors.lastname: Tomasikova
authors.forename: Eva
authors.initials: E
authors.lastname: Necesalova
authors.forename: Iva
authors.initials: I
authors.lastname: Zambo
authors.forename: Dagmar
authors.initials: D
authors.lastname: Kantorova
authors.forename: Iva
authors.initials: I
authors.lastname: Slamova
authors.forename: Vladimira
authors.initials: V
authors.lastname: Vranova
authors.forename: Dita
authors.initials: D
authors.lastname: Zezulkova
authors.forename: Martina
authors.initials: M
authors.lastname: Pesakova
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Pavelka
authors.forename: Renata
authors.initials: R
authors.lastname: Veselska
authors.forename: Petr
authors.initials: P
authors.lastname: Kuglik
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Sterba
mesh_terms: D000293:Adolescent; D002528:Cerebellar Neoplasms / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase; D008297:Male; D008527:Medulloblastoma / Q000235:genetics*; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: C489427:MYC protein, human; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc