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. 2022 Jan 30;9(2):56.
doi: 10.3390/vetsci9020056.

Molecular Genetic Investigation of Digital Melanoma in Dogs

David Conrad  1 , Alexandra Kehl  2 , Christoph Beitzinger  2 , Thomas Metzler  3 , Katja Steiger  3 , Nicole Pfarr  3 , Konrad Fischer  4 , Robert Klopfleisch  5 , Heike Aupperle-Lellbach  1
Affiliations

Molecular Genetic Investigation of Digital Melanoma in Dogs

David Conrad et al. Vet Sci. .

Abstract

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

Keywords: BRAF; CNV; KITLG; KRAS; NRAS; acral; c-kit; canine; mutation; tumour.

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Conflict of interest statement

N.P., Speaker Fee and Travelling Support: AstraZeneca, Illumina, Thermo Fisher Scientific, Roche, Bristol Myers Squibb; Advisory Boards: Bayer, Lilly, Novartis, Roche. K.S., Research Support: Roche; Advisory Board: TRIMT GmbH. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. The authors do offer diagnostic, genetic and pathology services.

Figures

Figure 1
Figure 1
Malignant melanoma of the fifth toe of the hindlimb of a 10-year-old Giant Schnauzer (Dog No. 48): (a) The claw horn has detached and the neoplastic tissue is exposed (arrow; © Dr. Blasberg, Kleintierpraxis Bad Honnef); (b) The claw bone shows significant osteolysis in the X-ray (circle; © Dr. Blasberg, Kleintierpraxis Bad Honnef); (c) Longitudinal cut of the formalin-fixed amputated digit with a 1.4 × 1.0 × 1.4 cm black mass (M) originating from the nailbed and infiltrating the bone (arrow); (d) Histologically, the neoplastic cells show varying degrees of pigmentation and infiltration of the bone (B) (HE, bar = 200 µm).
See this image and copyright information in PMC

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