BRAF Mutations in Canine Cancers

<div><p>Activating mutations of the <i>BRAF</i> gene lead to constitutive activation of the MAPK pathway. Although many human cancers carry the mutated <i>BRAF</i> gene, this mutation has not yet been characterized in canine cancers. As human and canine cancers share molecular abnormalities, we hypothesized that <i>BRAF</i> gene mutations also exist in canine cancers. To test this hypothesis, we sequenced the exon 15 of <i>BRAF</i>, mutation hot spot of the gene, in 667 canine primary tumors and 38 control tissues. Sequencing analysis revealed that a single 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 carcinoma (30/45, 67%). This mutation results in the amino acid substitution of glutamic acid for valine at codon 450 (V450E) of canine <i>BRAF</i>, corresponding to the most common <i>BRAF</i> mutation in human cancer, V600E. The evolutional conservation of the <i>BRAF</i> V600E mutation highlights the importance of MAPK pathway activation in neoplasia and may offer opportunity for molecular diagnostics and targeted therapeutics for dogs bearing <i>BRAF</i>-mutated cancers.</p>