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Wellcome Sanger Institute scientists compare genes in rare melanoma across humans, dogs and horses

Cancer genes in a rare type of melanoma have been compared for the first time in humans, dogs and horses by scientists at the Wellcome Sanger Institute and their collaborators.

A Dalmatian
A Dalmatian

The study offers insights into how cancer evolves across species and could help identify potential targets for new therapies.

The researchers sequenced the genomes of mucosal melanoma, a rare form of melanoma, which is a tumour type usually associated with skin cancer.

About 15,400 people are diagnosed with melanoma in the UK each year, and around one per cent of them will be diagnosed with mucosal melanoma.

It is a poorly understood subtype of the disease that arises from cells that produce pigment, known as melanocytes, found not only on skin but on mucosal surfaces of the body, such as the sinuses, nasal passages, mouth, vagina and anus.

The risk factors are unknown, with no known link to family history or UV exposure.

Patients often present late in the disease’s progression, with surgical removal of the tumour being the main treatment.

The cancer also affects dogs and horses, with varying outcomes.

Grey horses are genetically predisposed to melanoma
Grey horses are genetically predisposed to melanoma

Researchers at the Sanger Institute in Hinxton and University of Guelph in Canada analysed the genomes from mucosal melanoma tumours taken from 46 human, 65 canine and 28 equine melanoma tumours at the primary stage and found a handful of genes were mutated in all species.

The study is the first genomic experiment of such scale on dog tumours and the first to sequence horse tumours. Grey horses have a genetic predisposition to melanoma, but it does not usually spread, unlike in humans and dogs.

Dr David Adams, corresponding author from the Sanger Institute, said: “Genomics gives us a unique view into the hidden similarities and differences of cancer between species. The genetic changes, or mutations, we found in mucosal melanoma tumours across humans, dogs and horses suggests they are important enough to be conserved between species. These key mutations are likely to drive the cancer and could be targets for the development of new drugs.”

While immunotherapy has been used to treat some people with melanoma, it has not been effective for mucosal melanoma. The research suggests this may be because these tumours carry few mutations, so remain ‘hidden’ to the immune system and do not promote the immune response needed.

Kim Wong, first author from the Wellcome Sanger Institute, said: “Understanding the genetic changes underpinning mucosal melanoma suggests why people with this particular type of cancer may not benefit from immunotherapies.

A Labrador retriever with a vet
A Labrador retriever with a vet

“Genomics can help identify who is at greater risk of developing mucosal melanoma and provide information to genetic counsellors and doctors advising patients on disease management.”

Professor Geoffrey Wood, from the University of Guelph in Canada, said: “Spontaneous tumours in dogs are gaining recognition as ‘models’ of human cancers for the development of therapies that can benefit both species.

“This study shows the importance of understanding the genetic similarities and differences of cancers across species so that the most biologically relevant drug targets are prioritised.”

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