title: Real-time quantitative PCR analysis of pediatric ependymomas identifies novel candidate genes including TPR at 1q25 and CHIBBY at 22q12-q13.
abstract: Loss of chromosome 22 and gain of 1q are the most frequent genomic aberrations in ependymomas, indicating that genes mapping to these regions are critical in their pathogenesis. Using real-time quantitative PCR, we measured relative copy numbers of 10 genes mapping to 22q12.3-q13.33 and 10 genes at 1q21-32 in a series of 47 pediatric intracranial ependymomas. Loss of one or more of the genes on 22 was detected in 81% of cases, with RAC2 and C22ORF2 at 22q12-q13.1 being deleted most frequently in 38% and 32% of ependymoma samples, respectively. Combined analysis of quantitative-PCR with methylation-specific PCR and bisulphite sequencing revealed a high rate (>60% ependymoma) of transcriptional inactivation of C22ORF2, indicating its potential importance in the development of pediatric ependymomas. Increase of relative copy numbers of at least one gene on 1q were detected in 61% of cases, with TPR at 1q25 displaying relative copy number gains in 38% of cases. Patient age was identified as a significant adverse prognostic factor, as a significantly shorter overall survival time (P = 0.0056) was observed in patients <2 years of age compared with patients who were >2 years of age. Loss of RAC2 at 22q13 or amplification of TPR at 1q25 was significantly associated with shorter overall survival in these younger patients (P = 0.0492 and P = < 0.0001, respectively). This study identifies candidate target genes within 1q and 22q that are potentially important in the pathogenesis of intracranial pediatric ependymomas.
authors.affiliation: Department of Molecular Neuroscience, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, London, UK.
authors.forename: Katherine
authors.initials: K
authors.lastname: Karakoula
authors.forename: Blanca
authors.initials: B
authors.lastname: Suarez-Merino
authors.forename: Samantha
authors.initials: S
authors.lastname: Ward
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
authors.initials: J
authors.lastname: Beck
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; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D004806:Ependymoma / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D028861:Nuclear Pore Complex Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction / Q000379:methods; D011518:Proto-Oncogene Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C473750:CBY1 protein, human; D002352:Carrier Proteins; D004273:DNA, Neoplasm; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C073597:TPR protein, human