Alterations of Fas (Apo-1/CD95) gene in cutaneous malignant melanoma

Fas (Apo-1/CD95) is a cell-surface receptor involved in cell death signalin g, The key role of the Fas system in negative growth regulation has been st udied mostly within the immune system, and somatic mutations of Fas gene in cancer patients have been described solely in lymphoid-lineage malignancie s, However, many nonlymphoid tumor cells have been found to be resistant to Fas-mediated apoptosis, which suggests that Fas mutations, one of the poss ible mechanisms for Fas resistance, may be involved in the pathogenesis of nonlymphoid malignancies as well. In this study, we have analyzed the entir e coding region and all splice sites of the Fas gene for the detection of t he gene mutations in 44 human malignant melanomas in skin by polymerase cha in reaction, single-strand conformation polymorphism, and DNA sequencing. O verall, 3 tumors (6.8%) were found to have the Fns mutations, which were al l missense variants and identified in the cytoplasmic region (death domain) known to be involved in the transduction of an apoptotic signal, The data presented here suggest that somatic alterations of the Fns gene might Lad t o the loss of its apoptotic function and contribute to the pathogenesis of some human malignant melanomas.