Predisposition to Neoplastic Transformation Caused by Gene Replacement of H- ras 1

Homologous recombination was used to introduce a nominally transforming mutation into an endogenous H- ras 1 gene in Rat1 fibroblasts. Although both the mutant and the remaining normal allele were expressed equally, the heterozygous cells were not neoplastically transformed. Instead, spontaneously transformed cells arose from the heterozygotes at a low frequency, and the majority of these cells had amplified the mutant allele. Thus, the activated H- ras 1 allele was not by itself dominant over the normal allele but predisposed cells to transformation by independent events, such as amplification of the mutant allele.