RPS6KA4/MIR1237 and AURKC promoter regions are differentially methylated in Wilms' tumor.

Abstract

Wilms' tumor (WT) is the most frequent renal cancer in childhood, the occurrence of which is characterized by a relatively low frequency of associated mutations. While epigenetic alterations have been postulated to play a relevant role in the emergence of this tumor, the mechanisms involved in WT development remain largely unknown. In this study, the DNA methylation profile of WT was characterized with Beadchip array. Comparisons between WT with normal kidney identified 827 differentially methylated regions, most of which were attributable in hypermethylation in CpG islands. Among affected genes, WT1 and TP73 showed altered enhancers where hypermethylation was validaded by pyrosequencing. Thirty differentially methylated regions (DMRs) were identified in WT as compared to normal kidney, two of which were previously described. Two novel DMRs, located in RPS6KA4/MIR1237 and the AURKC promoter, were found to be hypermethylated in WT. Altogether, our data reinforced the relevance of alterations of DNA methylation in WT, highlighting the complex nature of these alterations that affect promoter regions as well as enhancers, UTRs and gene bodies.