Envoplakin, a possible candidate gene for focal NEPPK/esophageal cancer (TOC): The integration of genetic and physical maps of the TOC region on 17q25

Focal nonepidermolytic palmoplantar keratoderma (NEPPK), or tylosis, is an autosomal, dominantly inherited disorder of the skin that manifests as foca l thickening of the palmar and plantar surfaces. In three families studied, the skin disorder cosegregates with esophageal cancer and oral lesions. Ne w haplotype analysis, presented here, places the tylosis esophageal cancer (TOC) locus between D17S1839 and D17S785, Envoplakin (EVPL) is a protein co mponent of desmosomes and the cornified envelope that is expressed in epide rmal and esophageal keratinocytes and has been localized to the TOC region. Mutation analysis of EVPL in the three affected families failed to show ty losis-specific mutations, and haplotype analysis of three intragenic sequen ce polymorphisms of the EVPL gene placed it proximal to D17S1839, Confirmat ion of the exclusion of EVPL as the TOC gene by location was obtained by in tegration of the genetic and physical mapping data using radiation hybrid, YAC, BAC, and PAC clones. This new physical map will allow further identifi cation of candidate genes underlying NEPPK associated with esophageal cance r, which may also be implicated in the development of sporadic squamous cel l esophageal carcinoma and Barrett's adenocarcinoma. (C) 1999 Academic Pres s.