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Status |
Public on Dec 01, 2010 |
Title |
Comprehensive Mapping of Paediatric High Grade Glioma |
Organism |
Homo sapiens |
Experiment type |
Genome variation profiling by genome tiling array
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Summary |
Overall paediatric high grade glioma (pHGG) has a poor prognosis, in part due to the lack of understanding of the underlying biology. We therefore used high resolution 244k oligo array comparative genomic hybridisation (oligo aCGH) (Agilent Technologies) to analyse DNA from 38 formalin-fixed paraffin embedded pHGG samples, including 13 DIPG (ten pre-treatment samples and three post-mortem). The pattern of gains and losses were distinct from those seen in HGG arising in adults. In particular we found 1q gain in 22% of our cohort compared to 9% in adults. Homozygous loss at 8p12 was seen in 6/38 (15%) of pHGG. This deletion has not been previously reported in adult or paediatric high grade gliomas. The minimal deleted region is of the gene ADAM3A and homozygous deletion of ADAM3A was confirmed by quantitative real time PCR (qPCR). This novel homozygous deletion of ADAM3A in pHGG merits further study. Loss of CDKN2A/CDKN2B was seen in 4/38 (10%) samples by oligo a CGH, confirmed by FISH on TMAs and was restricted to supratentorial tumours. Amplification of the 4q11-13 region was detected in 8% of cases and included PDGFRA and KIT, subsequent qPCR analysis was consistent with amplification of PDGFRA. MYCN amplification was seen in 2/38 samples (5%) and was shown to be significantly associated with anaplastic astrocytomas (p=0.03). Overall DIPG shared similar spectrum of changes to supratentorial HGG with some notable differences including high frequency of 17p loss and 14q loss and lack of CDKN2A/CDKN2B deletion. To our knowledge, this study examines the largest DIPG cohort to date using high-throughput genetic techniques.
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Overall design |
38 high grade glioma samples including 13 DIPG (ten pre-treatment samples and three post-mortem) analysed by Agilent 244K array CGH. Samples BSG 1, 2, 3, 5, 6, 7, 8, 9, 10 and 11 are the ten pre-treatment DIPG samples. Samples BSG 4, 12 and 13 are the three post-treatment DIPG samples.
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Contributor(s) |
Barrow J |
Citation(s) |
21138945 |
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Submission date |
Apr 21, 2010 |
Last update date |
Oct 26, 2016 |
Contact name |
Jennifer Helen Barrow |
Organization name |
University of Nottingham, Children's Brain Tumour Research Centre
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Department |
Clinical Sciences
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Lab |
Medical School, D22
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Street address |
Queen's Medical Centre
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City |
Nottingham |
ZIP/Postal code |
NG7 2UH |
Country |
United Kingdom |
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Platforms (1) |
GPL4091 |
Agilent-014693 Human Genome CGH Microarray 244A (Feature number version) |
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Samples (38)
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Relations |
BioProject |
PRJNA126369 |
Supplementary file |
Size |
Download |
File type/resource |
GSE21420_RAW.tar |
1.9 Gb |
(http)(custom) |
TAR (of TXT) |
GSE21420_supplementary_files_readme.txt |
4.0 Kb |
(ftp)(http) |
TXT |
Processed data included within Sample table |
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