Alterations of Fas (Apo-1/CD95) gene in non-small cell lung cancer

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 non-lymphoid malignancies as well. In this study, we have analysed the enti re coding region and all splice sites of the Fns gene for the detection of the gene mutations in 65 human nonsmall cell lung cancers by polymerase cha in reaction, single strand conformation polymorphism and DNA sequencing. Ov erall, five tumors (7.7%) were found to have the I;as mutations, which were all missense mutations. Four of the five mutations identified were located in the cytoplasmic region (death domain) known to be involved in the trans duction of an apoptotic signal and one mutation was located in the transmem brane domain. This is the first report on the I;ns gene mutations in non-ly mphoid malignancies, and the data presented here suggests that alterations of the Fns gene might lead to the loss of its apoptotic function and contri bute to the pathogenesis of some human lung cancers.