Genomic deletions correlate with underexpression of novel candidate genes at six loci in pediatric pilocytic astrocytoma.
The molecular pathogenesis of pediatric pilocytic astrocytoma (PA) is not well defined. Previous cytogenetic and molecular studies have not identified nonrandom genetic aberrations. To correlate differential gene expression and genomic copy number aberrations (CNAs) in PA, we have used Affymetrix GeneChip HG_U133A to generate gene expression profiles of 19 pediatric patients and the SpectralChip 2600 to investigate CNAs in 11 of these tumors. Hierarchical clustering according to expression profile similarity grouped tumors and controls separately. We identified 1844 genes that showed significant differential expression between tumor and normal controls, with a large number clearly influencing phosphatidylinositol and mitogen-activated protein kinase signaling in PA. Most CNAs identified in this study were single-clone alterations. However, a small region of loss involving up to seven adjacent clones at 7q11.23 was observed in seven tumors and correlated with the underexpression of BCL7B. Loss of four individual clones was also associated with reduced gene expression including SH3GL2 at 9p21.2-p23, BCL7A (which shares 90% sequence homology with BCL7B) at 12q24.33, DRD1IP at 10q26.3, and TUBG2 and CNTNAP1 at 17q21.31. Moreover, the down-regulation of FOXG1B at 14q12 correlated with loss within the gene promoter region in most tumors. This is the first study to correlate differential gene expression with CNAs in PA.
Potter
Nicola
N
Department of Molecular Neuroscience, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, London, UK. n.potter@ion.ucl.ac.uk
Karakoula
Aikaterini
A
Phipps
Kim P
KP
Harkness
William
W
Hayward
Richard
R
Thompson
Dominic N P
DN
Jacques
Thomas S
TS
Harding
Brian
B
Thomas
David G T
DG
Palmer
Rodger W
RW
Rees
Jeremy
J
Darling
John
J
Warr
Tracy J
TJ
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D001254:Astrocytoma / Q000175:diagnosis / Q000235:genetics*; D001932:Brain Neoplasms / Q000175:diagnosis / Q000235:genetics*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D016000:Cluster Analysis; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D018628:Gene Dosage / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D015513:Oncogene Proteins / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics*; D017447:Receptors, Dopamine D1 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; C098982:BCL7A protein, human; C116387:BCL7B protein, human; C491323:CNTNAP1 protein, human; D015816:Cell Adhesion Molecules, Neuronal; C090173:FOXG1 protein, human; D051858:Forkhead Transcription Factors; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D015513:Oncogene Proteins; D011506:Proteins; D017447:Receptors, Dopamine D1; C107640:SH3GL2 protein, human