title: Cytogenetic analysis of paediatric astrocytoma using comparative genomic hybridisation and fluorescence in-situ hybridisation.
abstract: Little is known about the cytogenetic and molecular genetic events that lead to the formation of paediatric astrocytoma. We have analysed 57 paediatric astrocytoma (WHO grades I-IV) using comparative genomic hybridisation in order to identify common regions of abnormality. Large regions of copy number alterations were infrequent with 71% of tumours demonstrating no genomic imbalance. Furthermore, the most frequent aberrations (including gain of 6q, 2q, and 7q, and loss of 16 and 12q) occurred in only a subset of cases. High-copy number amplification was seen in five tumours at 12 different regions. The presence of copy number alterations was significantly associated with increasing grade of malignancy, and gain of 12q and the presence of high-copy number amplification were associated with a poor outcome in patients with malignant astrocytoma (P = 0.0039 and 0.0085, respectively). FISH analysis confirmed loss of 1p36 identified by CGH. There was no evidence of amplification of EGFR, CDK4, MET, CDK6, c-myc, or MDM2.
authors.affiliation: Department of Molecular Neuroscience, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, London, UK.
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Ward
authors.forename: Katherine
authors.initials: K
authors.lastname: Karakoula
authors.forename: Kim P
authors.initials: KP
authors.lastname: Phipps
authors.forename: William
authors.initials: W
authors.lastname: Harkness
authors.forename: Richard
authors.initials: R
authors.lastname: Hayward
authors.forename: Dominic
authors.initials: D
authors.lastname: Thompson
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Jacques
authors.forename: Brian
authors.initials: B
authors.lastname: Harding
authors.forename: John L
authors.initials: JL
authors.lastname: Darling
authors.forename: David G T
authors.initials: DG
authors.lastname: Thomas
authors.forename: Tracy J
authors.initials: TJ
authors.lastname: Warr
mesh_terms: D000293:Adolescent; D000704:Analysis of Variance; D001254:Astrocytoma / Q000145:classification / Q000235:genetics* / Q000401:mortality; D001932:Brain Neoplasms / Q000145:classification / Q000235:genetics* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D025063:Chromosome Disorders / Q000235:genetics; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D055028:Comparative Genomic Hybridization / Q000379:methods*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D007223:Infant; D008297:Male; D010372:Pediatrics; D016019:Survival Analysis; D055815:Young Adult