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Microarray analysis of pediatric
ependymoma identifies a cluster of 112 candidate genes including four
transcripts at 22q12.1-q13.3
Blanca Suarez-Merino,
Mike Hubank, Tamas Revesz, William Harkness, Richard Hayward, Dominic
Thompson, John L. Darling, David G.T. Thomas, and
Tracy J. Warr
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. Address correspondence to Tracy J. Warr,
Department of Molecular Neuroscience, Neuro-Oncology Group, Institute
of Neurology, Queen Square, London WC1N 3BG, UK
(T.Warr@ion.ucl.ac.uk).
Ependymomas are glial cell-derived
tumors characterized by varying degrees of chromosomal abnormalities
and variability in clinical behavior.
Cytogenetic analysis 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 interacting 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 22q12.313.3.
By Q-PCR we show that one of these genes, 7 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.
© 2005 Duke University Press
Source: http://hermia.ingentaselect.com/cgi-bin/linker?ini=dup_no&reqidx=/cw/dup/15228517/v7n1/s3/p20&user_id=undefined
DOI: http://dx.doi.org/10.1215/S1152851704000596)
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