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BRAF Mutations in Canine Cancers
Hiroyuki Mochizuki1, Katherine Kennedy1, Susan G Shapiro1
1Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, United States of America.
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.
Insights
BRAF gene mutations, common in human cancers, were identified in canine tumors. This discovery opens avenues for canine cancer diagnostics and targeted therapies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Activating BRAF mutations constitutively activate the MAPK pathway, a common event in human cancers.
- BRAF mutations are not yet characterized in canine cancers, despite shared molecular abnormalities between human and canine cancers.
Purpose of the Study:
- To investigate the presence and frequency of BRAF gene mutations in canine primary tumors.
- To determine if canine BRAF mutations mirror those found in human cancers, specifically the V600E mutation.
Main Methods:
- Sequencing of exon 15 of the BRAF gene, a known mutation hotspot.
- Analysis of 667 canine primary tumors and 38 control tissues.
Main Results:
- A BRAF mutation (T1349A, V450E) was identified in 9.6% (64/667) of canine tumors.
- High frequencies were observed in prostatic carcinoma (80%) and urothelial carcinoma (67%).
- The canine V450E mutation corresponds to the human V600E BRAF mutation.
Conclusions:
- The BRAF V450E mutation is present in canine cancers, analogous to the human V600E mutation.
- This finding underscores the significance of MAPK pathway activation in canine neoplasia.
- Identified mutations offer potential for developing molecular diagnostics and targeted therapeutics for canine cancers.
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