Hotspot Exon 15 Mutations in BRAF Are Uncommon in Feline Tumours

Area of Science:

• Oncology
• Molecular Biology
• Comparative Genomics

Background:

• The BRAF gene, encoding a key protein in the MAPK signaling pathway, is frequently mutated in various human and canine cancers.
• The BRAF V600E mutation is a known driver mutation in cancers like melanoma, thyroid carcinoma, and colorectal carcinoma.
• Given the conservation of BRAF across species and shared cancer pathways, its role in feline cancers was investigated.

Purpose of the Study:

• To investigate the frequency and type of BRAF mutations in a cohort of feline tumors.
• To determine if BRAF mutations are a significant driver in common feline cancers.
• To compare feline BRAF mutation profiles with those in human and canine cancers.

Main Methods:

• Development of primers to amplify exon 15 of the feline BRAF gene.
• Analysis of 196 feline tumors using Sanger sequencing of the PCR amplicon.
• Identification and characterization of BRAF mutations and variants.

Main Results:

• A single BRAF mutation (V597E), orthologous to canine and human hotspot mutations, was identified in one feline cutaneous melanoma.
• A common synonymous variant (BRAF T586T) was found in 23% of feline tumors, suspected to be a single nucleotide polymorphism.
• BRAF mutations were not frequent in the analyzed common feline tumors, including types that often harbor BRAF mutations in humans and dogs.

Conclusions:

• BRAF mutations are uncommon drivers in the studied feline tumor population.
• Feline cancer genomics, specifically BRAF mutational profiles, may not directly parallel human or canine counterparts.
• Further research is needed to understand the genetic landscape of feline cancers.