title: Downregulation of ST6GALNAC1 is associated with esophageal squamous cell carcinoma development.
abstract: Tylosis is an inherited disorder characterized by abnormal palmoplantar skin thickening and a highly elevated risk of esophageal squamous cell carcinoma (ESCC). Analyses of tylosis in families have localized the responsible gene locus to a region of chromosome 17q25.1. Frequent loss of heterozygosity (LOH) in 17q25.1 was also observed in the sporadic form of ESCC. A putative tumor suppressor gene for ESCC may exist at this locus. We investigated the expression patterns of genes on 17q25.1 in tumor and corresponding normal tissues from patients with sporadic ESCC using RNA sequence analysis. For candidate genes, quantitative real-time reverse transcription-PCR (qRT-PCR), direct sequence, LOH and methylation analyses were performed using 93 clinical ESCC samples and 10 cell lines. A significant downregulation of ST6GALNAC1 was demonstrated in ESCC tissues compared to its expression in normal tissues by qRT-PCR (n=93, p<0.0001). Frequent LOH (17/27, 62.9%) and hyper‑methylation in ST6GALNAC1 were also observed in all cell lines. Our results indicated that ST6GALNAC1 was downregulated in sporadic ESCC via hyper-methylation and LOH, and it may be a candidate responsible gene for ESCC. Furthermore, recent studies suggest that multiple genes on chromosome 17q25 are involved in ESCC development.
authors.affiliation: Department of Surgery, Iwate Medical University, Morioka, Iwate 020-8505, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iwaya
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka, University, Suita 565-0871, Japan.
authors.forename: Genta
authors.initials: G
authors.lastname: Sawada
authors.affiliation: Department of Surgery, Iwate Medical University, Morioka, Iwate 020-8505, Japan.
authors.forename: Suburu
authors.initials: S
authors.lastname: Amano
authors.affiliation: Department of Surgery, Iwate Medical University, Morioka, Iwate 020-8505, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Kume
authors.affiliation: Department of Surgery, Iwate Medical University, Morioka, Iwate 020-8505, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Ito
authors.affiliation: Department of Surgery, Iwate Medical University, Morioka, Iwate 020-8505, Japan.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Endo
authors.affiliation: Department of Surgery, Iwate Medical University, Morioka, Iwate 020-8505, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Konosu
authors.affiliation: Department of Surgery, Iwate Medical University, Morioka, Iwate 020-8505, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Shioi
authors.affiliation: Department of Surgery, Iwate Medical University, Morioka, Iwate 020-8505, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Akiyama
authors.affiliation: Department of Surgery, Iwate Medical University, Morioka, Iwate 020-8505, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Takahara
authors.affiliation: Department of Surgery, Iwate Medical University, Morioka, Iwate 020-8505, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Otsuka
authors.affiliation: Department of Surgery, Iwate Medical University, Morioka, Iwate 020-8505, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nitta
authors.affiliation: Department of Surgery, Iwate Medical University, Morioka, Iwate 020-8505, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Koeda
authors.affiliation: Department of Surgery, Iwate Medical University, Morioka, Iwate 020-8505, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Mizuno
authors.affiliation: Department of Surgery, Iwate Medical University, Morioka, Iwate 020-8505, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nishizuka
authors.affiliation: Department of Surgery, Iwate Medical University, Morioka, Iwate 020-8505, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Sasaki
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, Beppu 874-0838, Japan.
authors.forename: Koshi
authors.initials: K
authors.lastname: Mimori
mesh_terms: D000368:Aged; D063646:Carcinogenesis / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000235:genetics*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D060888:Real-Time Polymerase Chain Reaction; D012799:Sialyltransferases / Q000235:genetics*; D059467:Transcriptome
chemical_list: D012799:Sialyltransferases