title: Metaphase and array comparative genomic hybridization: unique copy number changes and gene amplification of medulloblastomas in South America.
abstract: Tumors of the central nervous system are the second most frequent malignancy of childhood, accounting for the majority of cancer-related deaths in this age group. Among these tumors, medulloblastomas (MB) remain in need of further genomic characterization toward understanding of pathogenesis and outcome predictors. Eight pediatric embryonal brain tumors were analyzed: five MB (one being desmoplastic), one PNET, one medulloepithelioma, and one ependymoblastoma. Analyses identified genomic imbalances, including the gain of 16p and the nonsyntenic coamplification of MYCN and TERT loci. More detailed FISH analysis showed that coamplification of MYCN and TERT in one of the MBs manifested as dispersed nuclear speckling, consistent with the presence of double minute chromosomes. There was considerable cell-to-cell copy number heterogeneity present, but it was clear that both genes were amplified concordantly. The amplification of oncogenes seems to play an important role in the pathogenesis of MB, and the association between MYCN and TERT amplifications and poor prognosis has not been well recognized. The uncharacteristic pattern of genomic imbalances detected in MB tumors may be a reflection of the characteristics of these tumors occurring in South America.
authors.affiliation: Applied Molecular Oncology, Ontario Cancer Institute, Princess Margaret Hospital, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada.
authors.forename: Maisa
authors.initials: M
authors.lastname: Yoshimoto
authors.forename: Jane
authors.initials: J
authors.lastname: Bayani
authors.forename: Paulo A S
authors.initials: PA
authors.lastname: Nuin
authors.forename: Nasjla S
authors.initials: NS
authors.lastname: Silva
authors.forename: Sergio
authors.initials: S
authors.lastname: Cavalheiro
authors.forename: João N
authors.initials: JN
authors.lastname: Stavale
authors.forename: Joyce A D
authors.initials: JA
authors.lastname: Andrade
authors.forename: Maria
authors.initials: M
authors.lastname: Zielenska
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Squire
authors.forename: Silvia R C
authors.initials: SR
authors.lastname: de Toledo
mesh_terms: D000293:Adolescent; D002528:Cerebellar Neoplasms / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D016259:Genes, myc; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D008527:Medulloblastoma / Q000235:genetics*; D008677:Metaphase; D013020:South America; D019098:Telomerase / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C509186:TERT protein, human; D019098:Telomerase