| Summary: | Canine digital melanoma, in contrast to canine oral melanoma, is still largely unexplored at the molecular genetic level. The aim of this study was to detect mutant genes in digital melanoma. Paraffin-embedded samples from 86 canine digital melanomas were examined for the <i>BRAF</i> V595E variant by digital droplet PCR (ddPCR), and for exon 11 mutations in <i>c-kit.</i> Furthermore, exons 2 and 3 of <i>KRAS</i> and <i>NRAS</i> were analysed by Sanger sequencing. Copy number variations (CNV) of <i>KITLG</i> in genomic DNA were analysed from nine dogs. The <i>BRAF</i> V595E variant was absent and in <i>c-kit</i>, a single nucleotide polymorphism was found in 16/70 tumours (23%). The number of copies of <i>KITLG</i> varied between 4 and 6. <i>KRAS</i> exon 2 codons 12 and 13 were mutated in 22/86 (25.6%) of the melanomas examined. Other mutually exclusive <i>RAS</i> mutations were found within the hotspot loci, i.e., <i>KRAS</i> exon 3 codon 61: 2/55 (3.6%); <i>NRAS</i> exon 2 codons 12 and 13: 2/83 (2.4%); and <i>NRAS</i> exon 3 codon 61: 9/86 (10.5%). However, no correlation could be established between histological malignancy criteria, survival times and the presence of <i>RAS</i> mutations. In summary, canine digital melanoma differs from molecular genetic data of canine oral melanoma and human melanoma, especially regarding the proportion of <i>RAS</i> mutations.
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