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Real-time quantitative PCR analysis of pediatric ependymomas identifies novel candidate genes including TPR at 1q25 and CHIBBY at 22q12-q13

Karakoula, K; Suarez-Merino, B; Ward, S; Phipps, KP; Harkness, W; Hayward, R; Thompson, D; ... Warr, TJ; + view all (2008) Real-time quantitative PCR analysis of pediatric ependymomas identifies novel candidate genes including TPR at 1q25 and CHIBBY at 22q12-q13. GENE CHROMOSOME CANC , 47 (11) 1005 - 1022. 10.1002/gcc.20607.

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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 ependynnomas. Increase of relative copy numbers of at least one gene on Iq 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. (c) 2008 Wiley-Liss, Inc.

Type: Article
Title: Real-time quantitative PCR analysis of pediatric ependymomas identifies novel candidate genes including TPR at 1q25 and CHIBBY at 22q12-q13
DOI: 10.1002/gcc.20607
Keywords: COMPARATIVE GENOMIC HYBRIDIZATION, TUMOR-SUPPRESSOR GENE, DEMONSTRATES FREQUENT LOSS, CHILDHOOD BRAIN-TUMORS, CHROMOSOMAL IMBALANCES, INTRACRANIAL EPENDYMOMAS, PROGNOSTIC-FACTORS, COPY NUMBER, EPIGENETIC INACTIVATION, BREAST CARCINOMAS
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health > ICH Development Bio and Cancer Prog
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health > ICH Developmental Neurosciences Prog
URI: http://discovery.ucl.ac.uk/id/eprint/178947
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