Aberrant Methylation of the 1p36 Tumor Suppressor Gene RIZ1 in Renal Cell Carcinoma

Background: Retinoblastoma protein-interacting zinc finger gene 1(RIZ1) functions as a tumor suppressor.Hypermethylation-mediated RIZ1 silencing has been reported in several cancers, but not in renal cell carcinoma(RCC) yet. Materials and
Methods: We examined the RIZ1 expression and methylation in a panel of RCC celllines and 50 primary tumors using semiquantitative/quantitative polymerase chain reaction (PCR), methylationspecific PCR, and bisulfite sequencing genomic. We also explored the relationship between methylation status ofRIZ1 and clinicopathological features in RCC patients.
Results: RIZ1 expression was down-regulated or lost inOS-RC-2, 769-P, Caki-1, 786-O and A498 RCC cell lines. Restored expression of RIZ1 was detected after additionof 5-aza-2’-deoxycytidine with/without trichostatin A, suggesting that DNA methylation directly mediates itssilencing. The RIZ1 expression was significantly reduced in RCCs compared to adjacent non-malignant renalsamples (P<0.001). Aberrant methylation was detected in 15 of 50 (30%) RCCs and in 2 of 28 (7%) adjacent nonmalignantrenal samples (P=0.02). No statistically significant correlation between methylated and unmethylatedcases with regard to age, gender, pathological stage and grade was observed.
Conclusions: RIZ1 expression isdown-regulated in human RCC, and this down-regulation is associated with methylation. RIZ1 methylation mayplay a role in renal carcinogenesis.