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BioMed Research International
Volume 2013 (2013), Article ID 181384, 7 pages
http://dx.doi.org/10.1155/2013/181384
Research Article

Downregulation of DLC-1 Gene by Promoter Methylation during Primary Colorectal Cancer Progression

1Department of Gastroenterology, Shanghai Changning District Cental Hospital, Shanghai 200336, China
2Department of Respiratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
3Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
4Central Laboratory, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
5Department of Nursing, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China

Received 16 July 2012; Revised 9 October 2012; Accepted 23 October 2012

Academic Editor: Colin Cooper

Copyright © 2013 Haixia Peng et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose. DLC-1 is a tumor suppressor gene frequently silenced in human cancers. However, the pathogenicity of DLC-1 epigenetic silencing in the mucosa-adenoma-carcinoma transformation process of colorectal cancer (CRC) has not been studied. Methods. Promoter methylation status of DLC-1 was evaluated in 4 human CRC cell lines, 48 normal mucosa, 57 adenomas, and 80 CRC tissues with methylation-sensitive high-resolution melting analysis (MS-HRMA), while the mRNA expression was examined by qPCR. HRMA was utilized to detect the KRAS codon 12, 13 and BRAF V600Emutations. Results. Partial (1%–10%) and extensive (10%–100%) DLC-1 promoter methylations were observed in 10% and 0% of normal mucosa, 46% and 14% of adenomas, and 60% and 36% of CRCs, respectively. The promoter methylation of DLC-1 was related with the reduction of gene expression and the advanced Duke’s stages (Stage C and D). DLC-1 promoter methylation and KRAS mutations are common concurrent pathological alternations. Conclusions. Epigenetic alternation plays a key role in the transcriptional silencing of DLC-1. It is also an independent risk factor related to the carcinogenesis of colorectal tumors and spans over its pathogenesis process. Therefore, DLC-1 promoter methylation quantitation may have a promising significance in the evaluation and management of CRC patients.