RESEARCH ARTICLE BRAF Mutations in Canine Cancers

Activating mutations of the BRAF gene lead to constitutive activation of the MAPK pathway. Although many human cancers carry the mutated BRAF gene, this mutation has not yet been characterized in canine cancers. As human and canine cancers share molecular ab-normalities, we hypothesized that BRAF gene mutations also exist in canine cancers. To test this hypothesis, we sequenced the exon 15 of BRAF, mutation hot spot of the gene, in 667 canine primary tumors and 38 control tissues. Sequencing analysis revealed that a sin-gle nucleotide T to A transversion at nucleotide 1349 occurred in 64 primary tumors (9.6%), with particularly high frequency in prostatic carcinoma (20/25, 80%) and urothelial carcino-ma (30/45, 67%). This mutation results in the amino acid substitution of glutamic acid for va-line at codon 450 (V450E) of canine BRAF, corresponding to the most common BRAF mutation in human cancer, V600E. The evolutional conservation of the BRAF V600E muta-tion highlights the importance of MAPK pathway activation in neoplasia and may offer op-portunity for molecular diagnostics and targeted therapeutics for dogs bearing BRAF-mutated cancers