Activated c-N-ras alleles have been detected in human lymphoma specimens. The aim of the present study was to determine the frequency of c-N-ras mutational activation in canine malignant lymphoma. DNA was isolated from 28 canine malignant lymphoma specimens collected from 28 separate dogs and examined for c-N-ras mutations by polymerase chain reaction amplification and direct sequencing. The tumors were naturally occurring and derived from 20 dogs with known exposures to the phenoxy herbicide 2,4-dichlo-rophenoxyacetic acid (2,4-D) and from 8 dogs with no known exposure to the herbicide. An oncogenically activating mutation was found in 1 dog without known 2,4-D exposure. The mutation was a 13th codon, second position transition that would result in a glycine-to-aspartate amino acid substitution. The results of this study demonstrate that, similar to the human, c-N-ras mutations are uncommon in dogs with malignant lymphoma and that there is no association between 2,4-D exposure and activation of c-N-ras in the dog.
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