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| Status |
Public on Oct 30, 2008 |
| Title |
Integrative Genome-wide Analysis of Glioblastoma. |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by genome tiling array
Expression profiling by genome tiling array
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| Summary |
Glioblastoma multiforme shows multiple chromosomal aberrations, the impact of which on gene expression remains unclear. To investigate this relationship and to identify putative initiating genomic events, we integrated a paired copy number and gene expression survey in glioblastoma using whole human genome arrays. Loci of recurrent copy number alterations were combined with gene expression profiles obtained on the same tumor samples. We identified a set of 406 ‘cis-acting DNA targeted genes’ corresponding to genomic aberrations with direct copy-number-driving changes in gene expression, defined as genes with either significantly concordant or correlated changes in DNA copy number and expression. Functional annotation revealed that these genes participate in key processes of cancer cell biology, providing insights into the genetic mechanisms driving glioblastoma. The robustness of the gene selection was validated on an external microarray data set including 81 glioblastomas and 23 non-neoplastic brain samples. The integration of array CGH and gene expression data highlights a robust ‘cis-acting DNA targeted genes’ signature that may be critical for glioblastoma progression, with two tumor suppressor genes PCDH9 and STARD13 that could be involved in tumor invasiveness and resistance to etoposide.
Keywords: Glioblastoma Multiforme, array CGH, microarray, data integration
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| Overall design |
Glioblastoma multiforme (n=19) and non-neoplastic brain samples (n=4) were analysed.
CGH-array were performed in a dye-swap experiment. Tumor DNA was hybridized with the corresponding patient blood DNA as reference to identify somatic changes only. Whole genome expression microarray were performed for the same GBMs with particular care to provide paired data sets.
For each brain tumor sample: a snap-frozen tumor block was cryodissected in 10µm sections. The first section as well as sections obtained every 100µm were stained to analyze tissue with at least 70 percents of tumoral cells and to exclude necrotic areas and widespread blood vessels. The adjacent sections were alternatively pooled in different tubes for RNA and DNA extractions, thus allowing a comparison between closely related biological materials.
The non-neoplastic brain samples (N) were also analysed by expression microarray to provide gene expression measurements expressed as log2 ratio (GBM vs mean N) and to allow testing procedure.
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| Contributor(s) |
de Tayrac M, Etcheverry A, Saïkali S, Aubry M, Hamlat A, Quillien V, Galibert M, Mosser J |
| Citation(s) |
18828157 |
| |
| Submission date |
Mar 18, 2008 |
| Last update date |
Jan 23, 2019 |
| Contact name |
Marie de Tayrac |
| E-mail(s) |
[email protected]
|
| Phone |
0223234776
|
| Organization name |
CNRS-UMR6061
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| Lab |
Regulation of transcription and oncogenesis
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| Street address |
2 avenue du Professeur Léon Bernard
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| City |
Rennes |
| ZIP/Postal code |
35000 |
| Country |
France |
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| Platforms (2) |
| GPL2879 |
Agilent-013282 Human Genome CGH Microarray 44B (Feature number version) |
| GPL6480 |
Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Probe Name version) |
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| Samples (60)
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| Relations |
| BioProject |
PRJNA107267 |
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