5468

PPARG

CIMT1|GLM1|NR1C3|PPARG1|PPARG2|PPARgamma;peroxisome proliferator-activated receptor gamma;PPARG;peroxisome proliferator-activated receptor gamma

PPAR gamma|PPAR-gamma|nuclear receptor subfamily 1 group C member 3|peroxisome proliferator-activated nuclear receptor gamma variant 1|peroxisome proliferator-activated receptor gamma 1

3p25

protein-coding

Epigenetic alterations, including methylation, have been shown to be an important mechanism of gene silencing in cancer. Ependymoma has been well characterized atthe DNA copy number and mRNA expression levels. However little is known about DNA methylation changes. To gain a more global view of the methylation profile of ependymoma we conducted an array-based analysis. Our data demonstrated tumors tosegregate according to their location in the CNS, which was associated with a difference in the global level of methylation. Supratentorial and spinal tumors displayed significantly more hypermethylated genes than posterior fossa tumors, similar to the 'CpG island methylator phenotype' (CIMP) identified in glioma andcolon carcinoma. This hypermethylated profile was associated with an increase inexpression of genes encoding for proteins involved in methylating DNA, suggesting an underlying mechanism. An integrated analysis of methylation and mRNA expression array data allowed us to identify methylation-induced expression changes. Most notably genes involved in the control of cell growth and death andthe immune system were identified, including members of the JNK pathway and PPARG. In conclusion, we have generated a global view of the methylation profileof ependymoma. The data suggests epigenetic silencing of tumor suppressor genes is an important mechanism in the pathogenesis of supratentorial and spinal, but not posterior fossa ependymomas. Hypermethylation correlated with a decrease in expression of a number of tumor suppressor genes and pathways that could be playing an important role in tumor pathogenesis.