Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Aug;184(2):731-7.
doi: 10.1016/j.juro.2010.03.108. Epub 2010 Jun 19.

Aberrant promoter methylation of DLEC1, a critical 3p22 tumor suppressor for renal cell carcinoma, is associated with more advanced tumor stage

Qian Zhang  1 , Jianming Ying, Jisheng Li, Yichao Fan, Fan Fong Poon, Ka Man Ng, Qian Tao, Jie Jin
Affiliations

Aberrant promoter methylation of DLEC1, a critical 3p22 tumor suppressor for renal cell carcinoma, is associated with more advanced tumor stage

Qian Zhang et al. J Urol. 2010 Aug.

Abstract

Purpose: Identifying tumor suppressor genes silenced by promoter CpG methylation uncovers mechanisms of tumorigenesis and identifies new epigenetic biomarkers for early cancer detection. DLEC1 is located at 3p22.3, a critical tumor suppressor gene locus for renal cell carcinoma. We explored its epigenetic alteration in renal cell carcinoma and possible clinicopathological association.

Materials and methods: We examined DLEC1 expression and methylation by semiquantitative reverse transcriptase and methylation specific polymerase chain reaction in 9 renal cell carcinoma cell lines and 81 primary tumors. We also analyzed the relationship between DLEC1 methylation and clinicopathological features in patients with renal cell carcinoma. We assessed DLEC1 inhibition of renal cell carcinoma cell growth by colony formation assay.

Results: DLEC1 methylation and down-regulation were detected in all renal cell carcinoma cell lines. Treatment with 5-aza-2'-deoxycytidine (Sigma) and/or trichostatin A (Cayman Chemical, Ann Arbor, Michigan) reversed methylation and restored DLEC1 expression, indicating that methylation directly mediates its silencing. Aberrant methylation was further detected in 25 of 81 primary tumors (31%) but only 1 of 53 nonmalignant renal tissues (2%) showed methylation. DLEC1 methylation status was significantly associated with TNM classification and grade in patients with renal cell carcinoma (chi-square test p = 0.01 and 0.04, respectively). DLEC1 ectopic expression in silenced renal cell carcinoma cells resulted in substantial tumor cell clonogenicity inhibition.

Conclusions: To our knowledge we report for the first time that DLEC1 is often down-regulated by CpG methylation and shows tumor inhibitory function in renal cell carcinoma cells, indicating its role as a tumor suppressor. DLEC1 tumor specific methylation may serve as a biomarker for early detection and prognosis prediction of this tumor.

PubMed Disclaimer

Publication types

Substances