Squamous cell carcinoma in a family with dominant dystrophic epidermolysisbullosa: a molecular genetic study

Squamous cell carcinoma (SCC) is a frequent complication in the severe, rec essively inherited forms of dystrophic epidermolysis bullosa (RDEB), howeve r, only rarely reported in dominant DEB. Although the SCCs in RDEB are freq uently well-differentiated by histopathology, they often have a poor progno sis due to multicentricity, rapid invasiveness, and development of distant metastases. In this study, we sought to determine the molecular basis of DD EB in a family with the unusual occurrence of SCCs. Specifically, a large D DEB family with 2 individuals being affected with SCC was analyzed for pote ntial mutations in the type VII collagen gene (COL7A1) by heteroduplex scan ning and direct nucleotide sequencing of PCR amplified segments of the gene . This mutation detection strategy disclosed a G-->A transition at nucleoti de position 6,235 which resulted in substitution of a glycine by arginine w ithin the collagenous region of COL7A1. This study establishes, for the fir st time, the molecular basis in a family with DDEB/SCC. Clinically, this st udy re-emphasizes the importance of vigilance in surveying DEB patients, no t only those with recessive but also with dominant inheritance, for SCC.