A novel mechanism of in vivo ras gene activation involving tandem duplication of coding sequences.

A series of weakly transforming c-K-ras genes have been detected in spontaneously occurring and chemically induced mouse adenomas. DNA sequence analysis of these weakly transforming ras oncogenes showed that activation occurred by a novel mechanism involving duplication of nine or ten codon segments flanking codon 61 in exon 2. The codon repetitions in exon 2 are directly preceded by a number of potentially recombinogenic DNA sequences which may have been involved in the genesis of the codon repetitions through mechanisms involving recombination or DNA slippage. Duplication of DNA sequences such as those observed in the mouse c-K-ras gene may represent a new mechanism for both tumor suppressor gene inactivation and proto-oncogene activation.