BRAF Mutations in Canine Cancers

PLoS One. 2015 Jun 8;10(6):e0129534. doi: 10.1371/journal.pone.0129534. eCollection 2015.


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 abnormalities, 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 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 BRAF, corresponding to the most common BRAF mutation in human cancer, V600E. The evolutional conservation of the BRAF V600E mutation highlights the importance of MAPK pathway activation in neoplasia and may offer opportunity for molecular diagnostics and targeted therapeutics for dogs bearing BRAF-mutated cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Base Sequence
  • Dogs
  • Exons / genetics
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation / genetics*
  • Neoplasms / genetics*
  • Neoplasms / veterinary*
  • Proto-Oncogene Proteins B-raf / chemistry
  • Proto-Oncogene Proteins B-raf / genetics*
  • Sequence Analysis, DNA


  • Proto-Oncogene Proteins B-raf