title: BRAF Mutations in Canine Cancers.
abstract: 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.
authors.affiliation: Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, United States of America.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mochizuki
authors.affiliation: Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, United States of America.
authors.forename: Katherine
authors.initials: K
authors.lastname: Kennedy
authors.affiliation: Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, United States of America.
authors.forename: Susan G
authors.initials: SG
authors.lastname: Shapiro
authors.affiliation: Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, United States of America; Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, North Carolina, United States of America; Center for Human Health and the Environment, North Carolina State University, Raleigh, North Carolina, United States of America; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: Matthew
authors.initials: M
authors.lastname: Breen
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001483:Base Sequence; D004285:Dogs; D005091:Exons / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics* / Q000662:veterinary*; D048493:Proto-Oncogene Proteins B-raf / Q000737:chemistry / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D048493:Proto-Oncogene Proteins B-raf