title: High-resolution array-based comparative genomic hybridization of medulloblastomas and supratentorial primitive neuroectodermal tumors.
abstract: Medulloblastomas and supratentorial primitive neuroectodermal tumors are aggressive childhood tumors. We report our findings using array comparative genomic hybridization (CGH) on a whole-genome BAC/PAC/cosmid array with a median clone separation of 0.97 Mb to study 34 medulloblastomas and 7 supratentorial primitive neuroectodermal tumors. Array CGH allowed identification and mapping of numerous novel, small regions of copy number change to genomic sequence in addition to the large regions already known from previous studies. Novel amplifications were identified, some encompassing oncogenes MYCL1, PDGFRA, KIT, and MYB not previously reported to show amplification in these tumors. In addition, one supratentorial primitive neuroectodermal tumor had lost both copies of the tumor-suppressor genes CDKN2A and CDKN2B. Ten medulloblastomas had findings suggestive of isochromosome 17q. In contrast to previous reports using conventional CGH, array CGH identified 3 distinct breakpoints in these cases: Ch 17: 17940393-19251679 (17p11.2, n = 6), Ch 17: 20111990-23308272 (17p11.2-17q11.2, n = 4), and Ch 17: 38425359-39091575 (17q21.31, n = 1). Significant differences were found in the patterns of copy number change between medulloblastomas and supratentorial primitive neuroectodermal tumors, providing further evidence that these tumors are genetically distinct despite their morphologic and behavioral similarities.
authors.affiliation: Department of Pathology, University of Cambridge, Division of Molecular Histopathology, UK. mcm41@cam.ac.uk
authors.forename: Martin Gerard
authors.initials: MG
authors.lastname: McCabe
authors.forename: Koichi
authors.initials: K
authors.lastname: Ichimura
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.forename: Karen
authors.initials: K
authors.lastname: Plant
authors.forename: L Magnus
authors.initials: LM
authors.lastname: Bäcklund
authors.forename: Danita M
authors.initials: DM
authors.lastname: Pearson
authors.forename: Vincent Peter
authors.initials: VP
authors.lastname: Collins
mesh_terms: D000293:Adolescent; D000328:Adult; D001932:Brain Neoplasms / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D020869:Gene Expression Profiling; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007223:Infant; D008527:Medulloblastoma / Q000235:genetics*; D018242:Neuroectodermal Tumors, Primitive / Q000235:genetics*; D009693:Nucleic Acid Hybridization / Q000379:methods*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015173:Supratentorial Neoplasms / Q000235:genetics*