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Series GSE19578 Query DataSets for GSE19578
Status Public on Jun 16, 2010
Title Integrated molecular genetic profiling of pediatric-high grade gliomas reveals key differences with adult disease
Organism Homo sapiens
Experiment type Genome variation profiling by SNP array
Expression profiling by array
Summary Purpose: To define copy number alterations and gene expression signatures underlying pediatric high-grade glioma (HGG). Patients and Methods: We conducted a high-resolution analysis of genomic imbalances in 78 de novo pediatric HGG, including 7 diffuse intrinsic pontine gliomas, and 10 HGG cases arising in children who received cranial irradiation for a previous cancer, using Affymetrix 500K GeneChips. Gene expression signatures for 53 tumors were analyzed with Affymetrix U133v2 arrays. Results were compared with publicly available data from adult tumors. Results: Pediatric and adult glioblastoma were clearly distinguished by frequent gain of chromosome 1q (30% vs 9%) and lower frequency of chromosome 7 gain (13% vs 74%), respectively. The most common focal amplifications also differed, with PDGFRA and EGFR predominant in childhood and adult populations respectively. These common alterations in pediatric HGG were detected at higher frequency in irradiation-induced tumors, suggesting that these are initiating events in childhood gliomagenesis. CDKN2A was the most common tumor suppressor gene targeted by homozygous deletion in pediatric HGG. No IDH1 hotspot mutations were found in pediatric tumors, highlighting molecular differences in pathogenesis between childhood HGG and adult secondary glioblastoma. Integrated copy number and gene expression data indicated that deregulated PDGFRA signaling plays a major role in pediatric HGG. Conclusions: Integrated molecular profiling showed substantial differences in the molecular features underlying pediatric and adult HGG, indicating that findings in adult tumors cannot be simply extrapolated to younger patients. PDGFRA may be a useful target for pediatric HGG including diffuse pontine gliomas.

Keywords: disease state analysis
 
Overall design 78 samples for SNP analysis, including 10 samples arising in children who received cranial irradiation for a previous cancer and 7 diffuse pontine gliomas; 53 of them with gene expression analysis; 2 tumor grades

To have access to SNP CEL files, please contact Dr. Suzanne Baker (suzzane.baker@stjude.org).
 
Contributor(s) Paugh BS, Qu C, Jones C, Liu Z, Adamowicz-Brice M, Zhang J, Bax DA, Coyle B, Barrow J, Hargrave D, Lowe J, Gajjar A, Zhao W, Broniscer A, Ellison DW, Grundy RG, Baker SJ
Citation(s) 20479398, 21659463, 24548782
Submission date Dec 18, 2009
Last update date Aug 22, 2019
Contact name Chunxu Qu
E-mail(s) chunxu.qu@stjude.org
Phone 9015952433
Organization name St Jude Children's Research Institute
Department Pathology
Lab Mullighan
Street address 262 Danny Thomas Pl
City Memphis
State/province TN
ZIP/Postal code 38105
Country USA
 
Platforms (3)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
GPL3718 [Mapping250K_Nsp] Affymetrix Mapping 250K Nsp SNP Array
GPL3720 [Mapping250K_Sty] Affymetrix Mapping 250K Sty2 SNP Array
Samples (209)
GSM487776 genomic DNA of GBM-HGG001, Glioblastoma, 5.8 years old
GSM487777 genomic DNA of GBM-HGG003, Glioblastoma, 6.5 years old
GSM487778 genomic DNA of GBM-HGG005, Glioblastoma, 16.5 years old
Relations
BioProject PRJNA122349

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE19578_RAW.tar 230.7 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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