Hotspot Exon 15 Mutations in BRAF Are Uncommon in Feline Tumours.

BRAF is one of multiple RAF proteins responsible for the activation of the MAPK cell signalling cascade involved in cell growth, differentiation, and survival. A hotspot BRAFV600E mutation, in exon 15, was determined to be a driver in 100% hairy cell leukaemias, 50%-60% of human melanomas, 30%-50% of human thyroid carcinomas and 10%-20% of human colorectal carcinomas. The orthologous BRAFV595E mutation was seen in 67% and 80% of canine bladder transitional cell carcinomas and prostatic adenocarcinomas, respectively. Since veterinary and human cancers exploit similar pathways and BRAF is highly conserved across species, BRAF can be expected to be a driver in a feline cancer. Primers were developed to amplify exon 15 of feline BRAF. One hundred ninety-six feline tumours were analysed. Sanger sequencing of the 211 bp PCR amplicon was done. A BRAF mutation was found in one tumour, a cutaneous melanoma. The mutation was a BRAFV597E mutation, orthologous to the canine and human hotspot mutations. A common synonymous variant, BRAFT586T, was seen in 23% (47/196) of tumours. This variant was suspected to be a single nucleotide polymorphism. BRAF was not frequently mutated in common feline tumours or in tumour types that frequently harbour BRAF mutations in human and canine cancers. As is seen in canine cancer genomics, the mutational profile in feline tumours may not parallel the histologic equivalent in human oncology.

A multi-institutional epidemiologic study evaluating environmental risk factors for feline oral squamous cell carcinoma.

Feline oral squamous cell carcinoma (FOSCC) is an aggressive cancer in domestic cats that has no effective treatment option when advanced. Preventative or early diagnostic measures are thus crucial. FOSCC is also a model for human head and neck SCC (HNSCC); strong risk factors in HNSCC include exposure to alcohol, tobacco, areca nut, and high-risk human papillomavirus. Previous studies have identified flea collar and tobacco smoke exposure, feeding canned tuna, canned cat food and cat foods with chemical additives, living in a rural environment, and having outdoor access as risk factors for FOSCC but there was no overlap in the risk factors between studies. In our study, risks for FOSCC were evaluated in an online epidemiologic survey study in 67 cats with FOSCC and 129 control cats. Clumping clay cat litter and flea collar use were significant risk factors for FOSCC on multiple logistic regression with odds ratios of 1.66 (95% CI 1.20-2.30) and 4.48 (95% CI 1.46-13.75) respectively. Crystalline silica is a carcinogen that may be present in all clay cat litters and tetrachlorvinphos is a carcinogen that is present in the most commonly used flea collars in our study. We recommend further investigation into the association between FOSCC and clay-based litter and/or flea collars containing tetrachlorvinphos.