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Highly recurrent BRAF p.V595E mutation in canine papillary oral squamous cell carcinoma
Authors:Santiago Peralta  Suzin M Webb  William P Katt  Jennifer K Grenier  Gerald E Duhamel
Institution:1. Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA;2. Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA;3. Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA
Abstract:Oral squamous cell carcinoma (OSCC) is the most common oral epithelial malignancy in dogs. It exhibits locally aggressive biological behaviour with the potential to metastasize, and a reported 1-year survival rate of 0% when left untreated. Expression studies suggest that aberrant MAPK signalling plays a key role in canine OSCC tumorigenesis, which is consistent with BRAF and HRAS MAPK-activating mutations reported in some tumours. Several morphological subtypes of canine OSCC have been described, with papillary, conventional, and basaloid as the most common patterns. We hypothesized that mutational differences may underlie these phenotypic variations. In this study, targeted Sanger sequencing and restriction fragment length polymorphism assays demonstrate that up to 85.7% of canine papillary OSCC (n = 14) harbour a BRAF p.V595E mutation. Assessment of neoplastic epithelial cell proliferation using Ki67 immunolabelling (n = 10) confirmed a relatively high proliferation activity, consistent with their known aggressive clinical behaviour. These findings underscore a consistent genetic feature of canine papillary OSCC and provide a basis for the development of novel diagnostic and targeted therapeutic approaches that can improve the quality of veterinary care.
Keywords:BRAF p  V595E  canine  Ki67  MAPK signalling  oral tumour  papillary oral squamous cell carcinoma  somatic mutation
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