Preferential and novel activation of H-ras in human bladder carcinomas

In a survey of primary human bladder carcinomas from 24 patients, using the NIH/3T3 transfection nude mouse tumor assay, we have detected an activated c-H-ras-1 gene in four cases. Two of these scored negative in primary transfections using a NIH/3T3 focus assay. Oligonucleotide analysis of genomic and enzymatically amplified DNA revealed substitution of valine at codon 12 in DNA from three transfectants and their parental carcinomas, which was absent from the DNA of normal tissue of each of these patients. The fourth activation was identified as a cysteine substitution at codon 13, a novel activation of c-H-ras-1 in a solid tumor sample. Thus, all seven activated ras genes reported in human urothelial tumors (Fujita et al., Proc. Natl. Acad. Sci. USA 82, 3849-3853, 1985) have been c-H-ras-1 genes, strongly suggesting that this member of the ras gene family is preferentially activated in cells of transitional origin.