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http://dx.doi.org/10.7314/APJCP.2015.16.9.4071

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

Ge, Peng (Department of Urology, Peking University First Hospital and Institute of Urology, Peking University)
Yu, Xi (Department of Urology, Peking University First Hospital and Institute of Urology, Peking University)
Wang, Zi-Cheng (Department of Urology, Peking University First Hospital and Institute of Urology, Peking University)
Lin, Jian (Department of Urology, Peking University First Hospital and Institute of Urology, Peking University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.16, no.9, 2015 , pp. 4071-4075 More about this Journal
Abstract
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 cell lines and 50 primary tumors using semiquantitative/quantitative polymerase chain reaction (PCR), methylation specific PCR, and bisulfite sequencing genomic. We also explored the relationship between methylation status of RIZ1 and clinicopathological features in RCC patients. Results: RIZ1 expression was down-regulated or lost in OS-RC-2, 769-P, Caki-1, 786-O and A498 RCC cell lines. Restored expression of RIZ1 was detected after addition of 5-aza-2'-deoxycytidine with/without trichostatin A, suggesting that DNA methylation directly mediates its silencing. The RIZ1 expression was significantly reduced in RCCs compared to adjacent non-malignant renal samples (P<0.001). Aberrant methylation was detected in 15 of 50 (30%) RCCs and in 2 of 28 (7%) adjacent non-malignant renal samples (P=0.02). No statistically significant correlation between methylated and unmethylated cases with regard to age, gender, pathological stage and grade was observed. Conclusions: RIZ1 expression is down-regulated in human RCC, and this down-regulation is associated with methylation. RIZ1 methylation may play a role in renal carcinogenesis.
Keywords
DNA methylation; RIZ1; tumor suppressor gene; kidney neoplasms; epigenetics;
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