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E-GEOD-22866 - DNA Methylation Profiling of Glioblastoma: Impact on Gene Expression and Clinical Outcome (Agilent Expression Study)

Status
Released on 19 January 2011, last updated on 7 August 2015
Organism
Homo sapiens
Samples (46)
Array (1)
Protocols (7)
Description
Genome-scale measurements of DNA methylation levels are necessary to decipher the epigenetic events involved in glioblastoma aggressive phenotype, and to guide new therapeutic strategies. In that purpose, we performed a whole genome integrative analysis of the methylation and expression profiles for 40 newly diagnosed glioblastoma patients. We have also screened for associations between CpG sites methylation levels and overall survival in a cohort of 50 patients uniformly treated with radiotherapy and chemotherapy with concomitant and adjuvant temozolomide (STUPP protocol). The methylation analysis identified 616 CpG sites differentially methylated between glioblastoma and control brain, a quarter being differentially expressed in a concordant way. Among these concordant CpG sites, 13 genes displayed, within our glioblastoma cohort, an inverse correlation between promoter methylation and expression levels: B3GNT5, FABP7, ZNF217, BST2, OAS1, SLC13A5, GSTM5, ME1, UBXD3, TSPYL5, FAAH, C7orf13, and C3orf14. The expression of these genes may be tightly regulated by epigenetic mechanisms. The survival analysis identified six CpG sites associated with overall survival. The SOX10 promoter methylation status (two CpG sites) stratifies the patients in a way similar to MGMT with improved performance based on Area Under the Curve criteria (0.78 vs. 0.71, p-value < 5.10-4). The methylation status of FNDC3B, TBX3, DGKI, and FSD1 promoters identify patients with MGMT methylated tumors non-responding to STUPP treatment (p-value < 1.10-4). These markers have a potential impact on therapeutic decision. 40 glioblastoma samples and 6 control brain samples were analysed. 2 distinct series of hybridizations were carried out, each containing GBMs and control brains.
Experiment type
transcription profiling by array 
Contacts
Amandine Etcheverry, Jean Mosser
Citation
DNA methylation in glioblastoma: impact on gene expression and clinical outcome. Etcheverry A, Aubry M, de Tayrac M, Vauleon E, Boniface R, Guenot F, Saikali S, Hamlat A, Riffaud L, Menei P, Quillien V, Mosser J. , PMID:21156036
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-22866.idf.txt
Sample and data relationshipE-GEOD-22866.sdrf.txt
Raw data (2)E-GEOD-22866.raw.1.zip, E-GEOD-22866.raw.2.zip
Processed data (1)E-GEOD-22866.processed.1.zip
Array designA-AGIL-28.adf.txt
Links