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Pediatric Neuro-Oncology |
Department of Molecular Neuroscience (B.S.-M., T.R., T.J.W.) and Division of Neurosurgery (D.G.T.T.), Institute of Neurology, National Hospital for Neurology and Neurosurgery, and Department of Molecular Haematology, Institute of Child Health (M.H.), University College London, London; Department of Neurosurgery, Great Ormond Street Hospital for Sick Children NHS Trust, London (W.H., R.H., D.T.); Research Institute in Healthcare Science, University of Wolverhampton, Wolverhampton (J.L.D.); UK
3 Address correspondence to Tracy J. Warr, Department of Molecular Neuroscience, Neuro-Oncology Group, Institute of Neurology, Queen Square, London WC1N 3BG, UK (T.Warr{at}ion.ucl.ac.uk).
Abstract
Ependymomas are glial cell-derived tumors characterized by varying degrees of chromosomal abnormalities and variability in clinical behavior. Cytogenetic analy-sis of pediatric ependymoma has failed to identify consistent patterns of abnormalities, with the exception of monosomy of 22 or structural abnormalities of 22q. In this study, a total of 19 pediatric ependymoma samples were used in a series of expression profiling, quantitative real-time PCR (Q-PCR), and loss of heterozygosity experiments to identify candidate genes involved in the development of this type of pediatric malignancy. Of the 12,627 genes analyzed, a subset of 112 genes emerged as being abnormally expressed when compared to three normal brain controls. Genes with increased expression included the oncogene WNT5A; the p53 homologue p63; and several cell cycle, cell adhesion, and proliferation genes. Underexpressed genes comprised the NF2 interact-ing gene SCHIP-1 and the adenomatous polyposis coli (APC)-associated gene EB1 among others. We validated the abnormal expression of six of these genes by Q-PCR. The subset of differentially expressed genes also included four underexpressed transcripts mapping to 22q12.3-13.3. By Q-PCR we show that one of these genes, CBX7 (22q13.1), was deleted in 55% of cases. Other genes mapping to cytogenetic hot spots included two overexpressed and three underexpressed genes mapping to 1q31-41 and 6q21-q24.3, respectively. These genes represent candidate genes involved in ependymoma tumorigenesis. To the authors' knowledge, this is the first time microarray analysis and Q-PCR have been linked to identify heterozygous/homozygous deletions.
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