title: Epigenetic silencing of checkpoint with fork-head associated and ring finger gene expression in esophageal cancer.
abstract: Checkpoint with fork-head associated and ring finger (CHFR) is a mitotic checkpoint gene with tumor-suppressor functions. Previous studies have described the hypermethylation of the CpG island in the promoter region as a key mechanism involved in silencing tumor suppressor genes. The epigenetic alterations regulating CHFR expression and the clinical significance of CHFR downregulation remain unclear. A total of 40 patients with esophageal squamous cell carcinoma who underwent primary resection were enrolled in this study. CHFR mRNA expression was quantified, followed by an evaluation of the methylation status using methylation-specific polymerase chain reaction (MSP) techniques in 29 patients. The correlation between CHFR expression and MSP status was then analyzed. In addition, the significance of CHFR expression was determined, with respect to clinicopathological features and overall survival. Aberrant hypermethylation of the CHFR gene was observed in 13 of 29 primary esophageal cancers. The CHFR expression levels of the methylated status samples was significantly lower than that of the unmethylated status samples (P=0.014). CHFR expression levels did not exhibit clinical significance with respect to the patient characteristics or overall survival. Hypermethylation of the CHFR gene is a common event in the development of primary esophageal cancer. CpG island hypermethylation of the promoter region in the CHFR gene is a key mechanism involved in silencing the CHFR gene in patients with esophageal cancer.
authors.affiliation: Department of Surgery, Hiratsuka Kyosai Hospital, Hiratsuka, Kanagawa 254-8502, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Molecular Pathology and Genetics Division, Kanagawa Cancer Center, Yokohama, Kanagawa 241-0815, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Miyagi
authors.affiliation: Department of Surgery, Yokohama City University, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Yukawa
authors.affiliation: Department of Surgery, Yokohama City University, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Rino
authors.affiliation: Department of Surgery, Yokohama City University, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Munetaka
authors.initials: M
authors.lastname: Masuda
keywords: checkpoint with fork-head associated and ring finger; esophageal cancer; methylation-specific polymerase chain reaction