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

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...

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Bibliographic Details
Published in:Genes chromosomes & cancer 2008-11, Vol.47 (11), p.1005-1022
Main Authors: Karakoula, Katherine, Suarez-Merino, Blanca, Ward, Samantha, Phipps, Kim P., Harkness, William, Hayward, Richard, Thompson, Dominic, Jacques, Thomas S., Harding, Brian, Beck, John, Thomas, David G. T., Warr, Tracy J.
Format: Article
Language:English
Subjects:
Adolescent
Base Sequence
Biomarkers, Tumor - genetics
Brain Neoplasms - genetics
Carrier Proteins - genetics
Child
Child, Preschool
Chromosomes, Human, Pair 1 - genetics
Chromosomes, Human, Pair 22 - genetics
DNA, Neoplasm - genetics
Ependymoma - genetics
Female
Gene Dosage
Humans
In Situ Hybridization, Fluorescence
Infant
Male
Molecular Sequence Data
Nuclear Pore Complex Proteins - genetics
Nuclear Proteins - genetics
Oligonucleotide Array Sequence Analysis
Polymerase Chain Reaction - methods
Proto-Oncogene Proteins - genetics
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Summary: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. 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. © 2008 Wiley‐Liss, Inc.
ISSN:1045-2257
1098-2264
DOI:10.1002/gcc.20607