DCC promoter hypermethylation in esophageal squamous cell carcinoma

Hannah Lui Park, Sook Kim Myoung, Keishi Yamashita, William Westra, Andre Lopes Carvalho, Juna Lee, Wei Wen Jiang, Hyen Baek Jin, Junwei Liu, Motonobu Osada, Chul So Moon, Joseph A. Califano, Masaki Mori, David Sidransky

Research output: Contribution to journalArticle

Abstract

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 quamous 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.

Original languageEnglish (US)
Pages (from-to)2498-2502
Number of pages5
JournalInternational Journal of Cancer
Volume122
Issue number11
DOIs
Publication statusPublished - Jun 1 2008

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Keywords

  • DCC
  • Epigenetic
  • Esophageal squamous cell carcinoma
  • Hypermethylation
  • Methylation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Park, H. L., Myoung, S. K., Yamashita, K., Westra, W., Carvalho, A. L., Lee, J., ... Sidransky, D. (2008). DCC promoter hypermethylation in esophageal squamous cell carcinoma. International Journal of Cancer, 122(11), 2498-2502. https://doi.org/10.1002/ijc.23434