DCC promoter hypermethylation in esophageal squamous cell carcinoma
Article first published online: 26 FEB 2008
Copyright © 2008 Wiley-Liss, Inc.
International Journal of Cancer
Volume 122, Issue 11, pages 2498–2502, 1 June 2008
How to Cite
Lui Park, H., Sook Kim, M., Yamashita, K., Westra, W., Lopes Carvalho, A., Lee, J., Jiang, W.-W., Hyen Baek, J., Liu, J., Osada, M., Moon, C.-S., Califano, J. A., Mori, M. and Sidransky, D. (2008), DCC promoter hypermethylation in esophageal squamous cell carcinoma. Int. J. Cancer, 122: 2498–2502. doi: 10.1002/ijc.23434
- Issue published online: 25 MAR 2008
- Article first published online: 26 FEB 2008
- Manuscript Accepted: 6 DEC 2007
- Manuscript Received: 6 JUL 2007
- esophageal squamous cell carcinoma;
Deleted in Colorectal Cancer (DCC) is a putative tumor suppressor gene, whose loss has been implicated in colorectal tumorigenesis. Decreased or loss of DCC expression has been demonstrated in a number of human cancers, including esophageal cancer. In this study, we analyzed esophageal squamous cell carcinoma (ESCC) cell lines and primary ESCCs as well as normal esophageal tissues for DCC methylation by bisulfite sequencing, methylation-specific PCR (MSP) and/or quantitative methylation-specific PCR (qMSP). When a qMSP cut-off value for positivity was set to 1.0, DCC methylation was detected in 10 of 12 ESCC cell lines tested, 74% of primary ESCCs (n = 70), 0% of corresponding normal esophageal tissues (n = 20) and 0% of normal esophagus from healthy individuals (n = 19). DCC expression was undetectable in the majority of ESCC cell lines, and treatment with the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine reactivated gene expression. DCC overexpression suppressed colony formation in ESCC cell lines, suggesting that DCC may function as a tumor suppressor gene in the esophagus. However, DCC methylation was not associated with any clinical or pathologic parameters measured. We have demonstrated that DCC methylation is a frequent and cancer-specific event in primary ESCCs, suggesting that DCC and associated pathways may represent a new diagnostical therapeutic target. © 2008 Wiley-Liss, Inc.