Gender difference in methylation of 5’-region of DUSP9 in clear-cell carcinoma of kidney

The DUSP9 gene, located on chromosome Xq28, encodes a dual specificity protein phosphatase MKP-4. A recent study could indicate a tumor suppression function of this phosphatase. Previously, we have shown the down-regulation of DUSP9 expression in renal clear cell carcinomas, but the mechanism of DUSP9 silencing is unclear. It is known that aberrant promoter hypermethylation of tumor suppressor genes occurs frequently during the pathogenesis of human cancer. In this study we explored whether the methylation of DUSP9 CpG sites is associated with loss of DUSP9 expression. Using combined bisulfite restriction analysis (COBRA) we compared methyation status of 5' region of DUSP9 in 27 paired tissue samples obtained from primary kidney tumors and corresponding normal tissues (18 samples were from male and 9 samples were from female patients). We have found the gender difference tn methylation of 5' region of DUSP9 in renal tumors.The increased methylation in tumor samples compared to paired normal samples were detected in 58% of the female patients (8/9), whereas all 18 male patients samples had unmethylated DNA status. Our results suggest that methylation of DUSP9 CpC sites may be associated with the loss of expression of this gene in kidney cancer cells. However, since the methylation frequency was low in male patients we concluded that the epigenetic silencing of DUSP9 by DNA methylation is not common and other mechanisms could be responsible for the loss of the expression of this gene in primary clear cell renal tumors.