title: Infrequent mutation of the human envoplakin gene is closely linked to the tylosis oesophageal cancer locus in sporadic oesophageal squamous cell carcinomas.
abstract: Envoplakin (EVPL) is a member of the desmosomal plaque proteins attached to desmosomal cadherin and keratin filaments. The EVPL gene has been mapped to the tylosis oesophageal cancer (TOC) locus on chromosome 17q25, where it has been demonstrated to be frequently deleted in both familial and sporadic forms of oesophageal squamous cell carcinoma (OSC). In this study, we examined EVPL gene mutations in 10 OSC cell lines and 20 sporadic OSCs using reverse transcription-polymerase chain reaction single-strand conformational analysis (RT-PCR SSCP) followed by direct sequencing. We observed one somatic mutation (GCG to ACG at codon 1104, Ala to Thr: 1/20, 5%) in the central rod domain and 5 intragenic polymorphic sites, where frequent loss of heterozygosity (LOH) (63%) was detected. No mutations were detected in the OSC cell lines. The rate of EVPL gene mutation was quite low in contrast to the frequency of LOH on the TOC locus in sporadic OSCs, and the high incidence of oesophageal cancer development in tylosis families. Our results suggest that EVPL might not be the target gene responsible for OSC, despite its strong candidacy in terms of character and localization.
authors.affiliation: Department of Pathology, Iwate Medical University School of Medicine, Uchimaru 19-1, Morioka 020-8505, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iwaya
authors.forename: Chihaya
authors.initials: C
authors.lastname: Maesawa
authors.forename: Toshimoto
authors.initials: T
authors.lastname: Kimura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ogasawara
authors.forename: Kenichro
authors.initials: K
authors.lastname: Ikeda
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kimura
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Noda
authors.forename: Kaoru
authors.initials: K
authors.lastname: Ishida
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Sato
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Saito
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Masuda
mesh_terms: D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D003062:Codon; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000235:genetics*; D005091:Exons; D008040:Genetic Linkage; D006801:Humans; D015776:Keratoderma, Palmoplantar, Diffuse / Q000235:genetics*; D019656:Loss of Heterozygosity; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology*; D018895:Microsatellite Repeats; D008957:Models, Genetic; D009154:Mutation; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D011487:Protein Conformation; D011498:Protein Precursors / Q000235:genetics* / Q000502:physiology*; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013997:Time Factors
chemical_list: D003062:Codon; D017931:DNA Primers; D018076:DNA, Complementary; D008565:Membrane Proteins; D011498:Protein Precursors; C100754:envoplakin