BACKGROUND: Changes in promoter DNA methylation pattern of genes involved in key 
biological pathways have been reported in glioblastoma. Genome-wide assessments 
of DNA methylation levels are now required to decipher the epigenetic events 
involved in the aggressive phenotype of glioblastoma, and to guide new treatment 
strategies.
RESULTS: We performed a whole-genome integrative analysis of methylation and 
gene expression profiles in 40 newly diagnosed glioblastoma patients. We also 
screened for associations between the level of methylation of CpG sites and 
overall survival in a cohort of 50 patients uniformly treated by surgery, 
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 of which was 
differentially expressed in a concordant way. Thirteen of the genes with 
concordant CpG sites displayed an inverse correlation between promoter 
methylation and expression level in glioblastomas: B3GNT5, FABP7, ZNF217, BST2, 
OAS1, SLC13A5, GSTM5, ME1, UBXD3, TSPYL5, FAAH, C7orf13, and C3orf14. Survival 
analysis identified six CpG sites associated with overall survival. SOX10 
promoter methylation status (two CpG sites) stratified patients similarly to 
MGMT status, but with a higher Area Under the Curve (0.78 vs. 0.71, p-value < 
5e-04). The methylation status of the FNDC3B, TBX3, DGKI, and FSD1 promoters 
identified patients with MGMT-methylated tumors that did not respond to STUPP 
treatment (p-value < 1e-04).
CONCLUSIONS: This study provides the first genome-wide integrative analysis of 
DNA methylation and gene expression profiles obtained from the same GBM cohort. 
We also present a methylome-based survival analysis for one of the largest 
uniformly treated GBM cohort ever studied, for more than 27,000 CpG sites. We 
have identified genes whose expression may be tightly regulated by epigenetic 
mechanisms and markers that may guide treatment decisions.