Somatic mutations of Fas (Apo-1/CD95) gene in cutaneous squamous cell carcinoma arising from a burn scar

Fas (Apo-1/CD95) is a cell-surface receptor involved in cell death signalin g, and recent reports have suggested that defects within the Fas receptor p athway such as Fas mutation play an important part in the development and p rogression of human tumors. Burn scar-related squamous cell carcinoma of sk in is a unique subtype of cutaneous squamous cell carcinoma, and tends to b e more aggressive in nature than conventional squamous cell carcinoma. The molecular mechanisms underlying the development and progression of burn sca r-related squamous cell carcinoma, however, are not clear. In this study, w e analyzed the entire coding region and all splice sites of the Fas gene fo r the detection of the somatic mutations in a series of 50 conventional squ amous cell carcinomas and 21 burn scar-related squamous cell carcinomas by polymerase chain reaction, single strand conformation polymorphism, and DNA sequencing. We detected mis-sense mutations in three of 21 burn scar-relat ed squamous cell carcinomas (14.3%), whereas no mutation was detected in 50 conventional squamous cell carcinomas. Of the three Fas mutations detected in the burn scar-related squamous cell carcinomas, one was found in Fas li gand-binding domain, another one was identified in the death domain known t o be involved in the transduction of an apoptotic signal, and the other one was found in the transmembrane domain. Our data show that some burn scar-r elated squamous cell carcinomas have Fas gene mutations in important region s for the apoptosis function and suggest that these mutations might be invo lved in the pathogenesis of burn scar-related squamous cell carcinomas. In addition, our results provide an important clue to understanding the differ ence between burn scar-related squamous cell carcinoma and conventional squ amous cell carcinoma at the molecular level.