BRAF Mutations in Canine Cancers

• Published in: PloS one Vol. 10; no. 6; p. e0129534
• Main Authors: Mochizuki, Hiroyuki, Kennedy, Katherine, Shapiro, Susan G, Breen, Matthew
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 08.06.2015; Public Library of Science (PLoS)
• Subjects: Abnormalities; Acids; Activation; Amino Acid Sequence; Amino Acid Substitution; Analysis; Animals; Base Sequence; Bladder cancer; Cancer; Conservation; Deoxyribonucleic acid; DNA; Dogs; Exons - genetics; Female; Gene mutation; Gene sequencing; Genes; Genetic aspects; Genetic Predisposition to Disease; Glutamate; Glutamic acid; Humans; Kinases; Leukemia; Male; MAP kinase; Medical diagnosis; Medical research; Melanoma; Metastasis; Molecular chains; Molecular Sequence Data; Mutation; Mutation - genetics; Mutation hot spots; Neoplasms - genetics; Neoplasms - veterinary; Oncology; Prostate cancer; Proto-Oncogene Proteins B-raf - chemistry; Proto-Oncogene Proteins B-raf - genetics; Sequence Analysis, DNA; Signal transduction; Squamous cell carcinoma; Tissue analysis; Transversion; Tumors; Urothelial carcinoma; Valine; Veterinary colleges; Veterinary medicine; North Carolina; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0129534

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.