Epigenetic analysis of several candidate tumor suppressor genes in chromophobe type renal cell carcinomas

Renal Cell Carcinomas (RCCs) accounts for 80-85% of all renal cancers, the remaining 15-20% are generally urothelial cancers of renal pelvis. Chromophobe type renal cell carcinoma (chRCC) is observed in 5% of all RCCs. Promoter hypermethylation in several candidate tumor suppressor genes were determined in clear cell renal carcinoma patients, but the genes associated with chromophobe type RCC were not clearly determined. The aim of this study was to determine the metyhlation status of the CST6 and GREM1 genes, reported to be hypermetilated in clear cell renal carcinoma, in chromophobe type renal carcinoma. Bisulfite conversion was performed in DNA samples isolated from the paraffin embedded tumor tissues and adjacent normal tissues of 39 patients and afterwords Methylation Specific PCR (MS-PCR) was performed. The prevalence of GREM1 methylation in tumor tissues (51%) was found to be significantly higher than normal tissues (23%) [p=0.012, OR (%95CI)=3.51 (1.32-9.29)]. Similarly, CST6 methylation was also observed significantly higher in tumor tissues (23%) compared to the normal tissues (2%). [p=0.02, OR (%95CI)=11.4 (1.36-95.04)]. However, no significant association was determined between the metyhlation status and age, sex or pathological stage of patients (p>0.05). These results supported the idea that hypermethylation in CST6 and GREM1 genes may play role in the development of chromophobe type renal cell carcinoma.