Frequency of molecular alterations affecting ras protooncogenes in human urinary tract tumors.

Abstract

Members of the ras gene family are activated as oncogenes in many different human cancers. To systematically determine the frequency at which such genes might be involved in the neoplastic process affecting a specific target tissue, urothelial cells, a large series of urinary tract tumors for ras oncogenes were surveyed by DNA transfection and molecular genetic analysis. Harvey (Ha)-ras oncogenes were detected in 2 of 38 tumors by transfection, molecularly cloned in biologically active form, and shown to contain single base changes at condon 61 leading to substitutions of arginine and leucine, respectively, for glutamine at this position. One additional Ha-ras oncogene was identified in a bladder carcinoma by restriction polymorphisms at codon 12. In 1 of 21 tumors, a 40-fold amplification of the Kirsten (Ki)-ras gene was observed. No amplification of other ras genes was detected in any of the tumors analyzed. Codons 12 and 61 are the major hot spots of ras oncogene activation. Quantitative alterations in expression due to gene amplification may provide an alternative mechanism for ras gene activation in primary human tumors.