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 abnormalities, we hypothesized that BRAF gen...

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Bibliographic Details
Published in:PloS one 2015-06, Vol.10 (6), p.e0129534-e0129534
Main Authors: Mochizuki, Hiroyuki, Kennedy, Katherine, Shapiro, Susan G, Breen, Matthew
Format: Article
Language:English
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
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0129534