Mutational Landscape of KIT Proto-Oncogene Coding Sequence in 62 Canine Cutaneous and Subcutaneous Mast Cell Tumors

Canine mast cell tumors (MCTs) are common skin neoplasms with varying biological behaviors. The <i>KIT</i> proto-oncogene plays a key role in the development of these tumors, and internal tandem duplications on exon 11 are usually associated with more aggressive behavior, increased local recurrence, and decreased survival time. However, apart from exons 8-11 and 17, there is limited understanding of the overall <i>KIT</i> mutational landscape in canine MCTs. This work aims to analyze the entire <i>KIT</i> coding sequence (21 exons) in a cohort of 62 MCTs, which included 38 cutaneous and 24 subcutaneous tumors, and potentially identify new variants. In addition to confirming previously reported activating <i>KIT</i> mutations in exons 8, 9, and 11, we identified new variants in exons 2, 3, 5, 16, and the 3' untranslated region (UTR). Notably, these last variants include an amino acid change (Asp/His) in exon 16. Additionally, we confirmed a differential prevalence of <i>KIT</i> variants in cutaneous and subcutaneous MCTs. These findings enhance our understanding of the <i>KIT</i> proto-oncogene coding sequence and provide valuable information for future confirmatory studies.