The tylosis esophageal cancer (Toc) locus: more than just a familial cancer gene*

Abstract

Tylosis (focal non-epidermolytic palmoplantar keratoderma; NEPPK) is associated with esophageal cancer in three families, two of which contain six or seven generations. The causative locus, the tylosis esophageal cancer (TOC) gene, has been localized to a small region on chromosome 17q25. Recent loss of heterozygosity (LOH) studies have indicated a role for the TOC gene in sporadic squamous cell esophageal cancer and Barrett's adenocarcinoma. We have now integrated genetic and physical mapping data from the TOC region, based on microsatellite markers and radiation hybrid, yeast (YAC), bacterial (BAC) and P1 artificial chromosomal (PAC) clones, and formed a partial minimal contig of one non-chimeric YAC (330 kb) and one PAC. Twenty-three candidate genes, including envoplakin (EVPL), were mapped against this contig, but only one was shown to be located within the minimal region. This physical map will allow further characterization of the region and identification of a gene implicated in both familial and sporadic squamous cell esophageal carcinoma and Barrett's adenocarcinoma.

Cytoglobin: biochemical, functional and clinical perspective of the newest member of the globin family

“…Tylosis (palmoplantar keratoderma) manifestations include pathological thickening of the palmoplantar area of the skin frequently resulting from aberrant production of keratins and cohesion molecules [119]. TOC is an autosomal dominant hereditary disorder associated with higher risk of oesophageal cancer and oral lesions [120]. Chromosome mapping, which involved three affected families, revealed the minimal region (42.5 kb) responsible for TOC occurrence.…”

Dépistage du cancer épidermoïde de l’œsophage par endoscopie chez les sujets à risque élevé de cancer

“…Un risque de 95 % à l'âge de 70 ans existe dans une maladie autosomale dominante rare, la kératose palmoplantaire (tylose), liée à une anomalie du chromosome 9 (17q25) [37,38]. Le cancer survient dès 30 ans, et en moyenne à l'âge de 45 ans.…”

Prevention and management of early esophageal cancer

“…Furthermore, infection with the human papilloma virus has been implicated in endemic occurrences of SSC [9]. Other predisposing conditions include tylosis, a rare autosomal-dominant inherited disease that is also known as nonepidermolytic palmo-plantar hyperkeratosis and is associated with mutations of the TOC locus on chromosome 17q25 [10]. Patients with achalasia, an esophageal motility disorder that is characterized by abnormally high pressures of the lower esophageal sphincter, have been demonstrated to have an up to 140-fold increased risk for the development of SSC of the esophagus [11].…”