Frequent hypermethylation of a CTCF binding site influences Wilms tumor 1 expression in Wilms tumors

The Wilms tumor 1 (WT1) gene plays an essential role in early development and differentiation of the urinary tract, particularly the kidneys. Aberrant transcriptional activity of WT1 is a key finding in the genesis of Wilms tumors (WTs). However, the mechanisms responsible for this alteration remain poorly understood. In the present study, we examined the methylation pattern of a putative CCCTC-binding factor (CTCF) binding site downstream of the WT1 gene as a potential cause of WT1 misregulation in 44 native WT specimens. We found that 16 WT cases exhibited a much higher WT1 expression compared to normal kidney tissue, and that the high mRNA expression of WT1 is strongly correlated with a high degree of DNA methylation of the CTCF binding site near the WT1 promoter. However, there was no correlation between the KTS+/KTS- splicing variants of WT1 and the methylation status of the CpGs of the CTCF binding site. Our results demonstrated an aberrant methylation pattern at a CTCF binding site downstream the WT1 gene, which is associated with an elevated WT1 transcriptional activity. Thus, methylation of the CTCF binding site may be partially responsible for the transcriptional activation of the WT1 locus and hypermethylation of this site may be an important oncogenic mechanism in the genesis of WT.