title: Characterization of a 500 kb region on 17q25 and the exclusion of candidate genes as the familial Tylosis Oesophageal Cancer (TOC) locus.
abstract: The locus for a syndrome of focal palmoplantar keratoderma (Tylosis) associated with squamous cell oesophageal cancer (TOC) has been mapped to chromosome 17q25, a region frequently deleted in sporadic squamous cell oesophageal tumours. Further haplotype analysis described here, based on revised maps of marker order, has reduced the TOC minimal region to a genetic interval of 2 cM limited by the microsatellite markers D17S785 and D17S751. Partial sequence data and complete physical maps estimate the actual size of this region to be only 0.5 Mb. This analysis allowed the exclusion of proposed candidate tumour suppressor genes including MLL septin-like fusion (MSF), survivin, and deleted in multiple human cancer (DMC1). Computer analysis of sequence data from the minimal region identified 13 candidate genes and the presence of 50-70 other 'gene fragments' as ESTs and/or predicted exons and genes. Ten of the characterized genes were assayed for mutations but no disease-specific alterations were identified in the coding and promoter sequences. This region of chromosome 17q25 is, therefore, relatively gene-rich, containing 13 known and possibly as many as 50 predicted genes. Further mutation analysis of these predicted genes, and others possibly residing in the region, is required in order to identify the elusive TOC locus.
authors.affiliation: Molecular Genetics and Oncology Group, Department of Clinical Dental Sciences, The University of Liverpool, Liverpool L69 3GN, UK. j.m.risk@liverpool.ac.uk
authors.forename: Janet M
authors.initials: JM
authors.lastname: Risk
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Evans
authors.forename: Joanne
authors.initials: J
authors.lastname: Jones
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Langan
authors.forename: Lyn
authors.initials: L
authors.lastname: Rowbottom
authors.forename: Fiona E
authors.initials: FE
authors.lastname: McRonald
authors.forename: Helen S
authors.initials: HS
authors.lastname: Mills
authors.forename: Anthony
authors.initials: A
authors.lastname: Ellis
authors.forename: Joan M
authors.initials: JM
authors.lastname: Shaw
authors.forename: Irene M
authors.initials: IM
authors.lastname: Leigh
authors.forename: David P
authors.initials: DP
authors.lastname: Kelsell
authors.forename: John K
authors.initials: JK
authors.lastname: Field
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics*; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D004938:Esophageal Neoplasms / Q000209:etiology / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006801:Humans; D015776:Keratoderma, Palmoplantar, Diffuse / Q000209:etiology / Q000235:genetics*