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 sp ontaneously occurring and chemically induced mouse adenomas. DNA seque nce analysis of these weakly transforming ras oncogenes showed that ac tivation occurred by a novel mechanism involving duplication of nine o r ten codon segments flanking codon 61 in exon 2. The codon repetition s in exon 2 are directly preceded by a number of potentially recombino genic DNA sequences which may have been involved in the genesis of the codon repetitions through mechanisms involving recombination or DNA s lippage. Duplication of DNA sequences such as those observed in the mo use c-K-ras gene may represent a new mechanism for both tumor suppress or gene inactivation and proto-oncogene activation.