ABSENCE OF ACTIVATING MUTATIONS OF THE RAF1 PROTOONCOGENE IN HUMAN LUNG-CANCER

Recently, the RAF protein has been demonstrated to be a direct effecto r of RAS protein in a RAS-mediated signal transduction pathway. Activa tions of the RAF1 gene by small mutations, such as point mutations in the kinase domain and a tetrapeptide insertion into conserved region 2 , have been suggested from analyses of chemically induced lung cancers in mice and by site-directed mutagenesis. We investigated the presenc e of small mutations of the RAF1 gene in human lung carcinomas, especi ally in those not carrying the mutated RAS gene, expecting that aberra tions of the RAF1 gene might play a role complementary to RAS gene mut ations in tumorigenesis. Single-strand conformation polymorphism (SSCP ) analysis of polymerase chain reaction products of DNA samples from 1 40 patients revealed no tumor specific mutations of the RAF1 gene in a ny of these specimens. This result suggests that mutations of the RAF1 gene are not involved in tumorigenesis in human lung.