Melanoma: Cross-species Oncology Research Identifies New Therapeutic Targets

New Treatments

for a rare form of melanoma could result from the discovery of Similar genetic mutations in humans, dogs, and horses. In a study conducted on these three species in the United Kingdom, researchers performed the sequencing and comparative genomics of human mucosal melanoma, canine oral melanoma, and equine melanoma. They identified genetic similarities and differences that may influence tumor behavior and response to treatment.

Melanoma is a cancer that most often affects the skin, but a rarer subtype, called mucosal melanoma, occurs in humans in areas other than the skin, such as the anal or vaginal canal, and the nasal and oral cavities. In dogs, oral melanoma is much more common than in humans, and its prognosis is poor. It presents

histological similarities to the human disease and most often develops in the oral mucosa. In horses, melanoma is also located on or near the mucous membranes, but it is generally less aggressive. In all three species, the primary treatment is surgical removal of the tumor.

Published in *Nature Communications*, the study sequenced the exomes (parts of the genome that account for 85% of mutations) from 46 cases of human mucosal melanoma, 65 cases of canine oral melanoma, and 28 cases of equine melanoma, as well as corresponding healthy tissues. The goal was to characterize somatic mutations in melanoma across each species in order to conduct a comparative interspecies analysis of recurrent genetic mutations and copy number variability.

Most of the sequenced melanomas had fewer than five mutated genes, which is far fewer than in skin tumors. Since these mutations drive cancer development, they could be targeted in new treatments. With fewer mutations, this cancer may be more difficult for the immune system to detect. This could explain why current immunotherapy often fails to treat oral melanoma in dogs and mucosal melanoma in humans.

This study is the first to compare the genomes of human, canine, and equine melanomas; the first to perform sequencing on these cancerous tumors in horses; and the first to perform canine oral melanoma sequencing on this scale. Comparing cancers across species aims to identify the most biologically relevant therapies for each. This is a good example of the One Health approach.