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International journal of molecular sciences2025; 26(14); 6620; doi: 10.3390/ijms26146620

Gray-Horse Melanoma-A Wolf in Sheep’s Clothing.

Abstract: Malignant melanoma (MM) affects not only humans but also animals, with gray horses being particularly predisposed to acquiring the disease. Multiomics have greatly advanced the understanding of human MM. In contrasty little is known regarding the pathogenesis of gray-horse melanoma and the unique phenomenon of melanoma "dormancy" in some animals. To help close this gap in knowledge, melanoma tissue and intact skin collected from gray horses were subjected to transcriptome analysis using RNAseq. In the next step, cultured primary tumor cells and normal skin fibroblasts were established from gray horses, and their protein expression profiles were determined. The obtained data unambiguously identified gray-horse melanoma (ghM) as a malignant tumor, as reflected by the overrepresentation of pathways typically activated in human melanoma and other human cancers. These included the RAS/RAF/MAPK, the IRS/IGF1R, and the PI3K/AKT signaling networks. In addition, the obtained data suggest that the key molecules RAC1, RAS, and BRAF, which are frequently mutated in human melanoma, may also contain activating mutations in ghM, whilst PTEN may harbor loss-of-function mutations. This issue will be subject to downstream analyses determining the mutational status in ghM to further advance the understanding of this frequent disease in gray horses.
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Publication Date: 2025-07-10 PubMed ID: 40724880PubMed Central: PMC12295847DOI: 10.3390/ijms26146620Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research explores the malignant melanoma (MM) disease in gray horses, and the unique phenomenon of melanoma “dormancy” in these animals. The study used multiomics and transcriptome analysis using RNAseq on melanoma tissue and intact skin from gray horses. The findings suggest that gray-horse melanoma (ghM) share similarities with human melanoma and other human cancers, potentially offering insights for the treatment of both animal and human patients.

Study Objective and Methodology

  • This research was conducted to gain more understanding about the pathogenesis of gray-horse melanoma (ghM) and the unique pattern of melanoma “dormancy” in some animals. The researchers used multiomics, a field integrating data from genomics, proteomics, metabolomics and other -omics to understand complex biological systems.
  • The researchers collected melanoma tissue and intact skin from gray horses for a transcriptome analysis using RNAseq, a methodology used to determine the distinct RNAs within a biological sample at a specific moment. This methodology is particularly useful for identifying the diseases and conditions associated with different RNA patterns.
  • Next, primary tumor cells and normal skin fibroblasts (the most common cells in connective tissue in animals) were cultivated from the gray horses. Their protein expression profiles were then determined, offering information about gene expression and involvement in the disease.

Significant Findings

  • The data derived from the research unambiguously identified gray-horse melanoma (ghM) as a malignant tumor. This conclusion was drawn from the observation of overrepresentation of pathways commonly activated in human melanoma and other human cancers in ghM. These pathways included RAS/RAF/MAPK, IRS/IGF1R, and the PI3K/AKT signaling networks.
  • The data pointed to the possibility that key molecules, including RAC1, RAS, and BRAF (frequently mutated in human melanoma), may also contain activating mutations in ghM. The researchers also speculated that PTEN might harbor loss-of-function mutations in ghM.

Conclusion and Future Research

  • The findings from this study suggest parallels between ghM and human cancers, particularly human melanoma. This opens up the possibility of further research into whether therapies successful in treating human cancers might have a place in treating ghM in horses.
  • The research also identified potential future lines of inquiry, including determining the mutational status in ghM. This work could further increase the understanding of the frequent gray-horse melanoma, potentially informing more targeted and effective treatments for both gray horses and potentially, humans.

Cite This Article

APA
Brodesser DM, Schlangen K, Rodríguez-Rojas A, Kuropka B, Doulidis PG, Brandt S, Pratscher B. (2025). Gray-Horse Melanoma-A Wolf in Sheep’s Clothing. Int J Mol Sci, 26(14), 6620. https://doi.org/10.3390/ijms26146620

Publication

International journal of molecular sciences
ISSN: 1422-0067
NlmUniqueID: 101092791
Country: Switzerland
Language: English
Volume: 26
Issue: 14
PII: 6620

Researcher Affiliations

Brodesser, Daniela M
  • Research Group Oncology (RGO), Centre for Equine Health and Research, Department for Small Animals and Horses, University of Veterinary Medicine, Veterinaerplatz 1, 1210 Vienna, Austria.
Schlangen, Karin
  • Section for Biosimulation and Bioinformatics, Centre for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna (MUV), Waehringer Guertel 18-20, 1090 Vienna, Austria.
Rodríguez-Rojas, Alexandro
  • Division of Small Animal Internal Medicine, Department for Small Animals and Horses, University of Veterinary Medicine, Veterinaerplatz 1, 1210 Vienna, Austria.
Kuropka, Benno
  • Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.
Doulidis, Pavlos G
  • Division of Small Animal Internal Medicine, Department for Small Animals and Horses, University of Veterinary Medicine, Veterinaerplatz 1, 1210 Vienna, Austria.
Brandt, Sabine
  • Research Group Oncology (RGO), Centre for Equine Health and Research, Department for Small Animals and Horses, University of Veterinary Medicine, Veterinaerplatz 1, 1210 Vienna, Austria.
Pratscher, Barbara
  • Division of Small Animal Internal Medicine, Department for Small Animals and Horses, University of Veterinary Medicine, Veterinaerplatz 1, 1210 Vienna, Austria.

MeSH Terms

  • Animals
  • Melanoma / genetics
  • Melanoma / veterinary
  • Melanoma / metabolism
  • Melanoma / pathology
  • Horses
  • Skin Neoplasms / genetics
  • Skin Neoplasms / veterinary
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Signal Transduction
  • Horse Diseases / genetics
  • Horse Diseases / metabolism
  • Horse Diseases / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Gene Expression Profiling
  • Transcriptome
  • Mutation

Grant Funding

  • 2012 / Vienna's Spanish Riding School

Conflict of Interest Statement

The authors declare no conflicts of interest.

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Citations

This article has been cited 1 times.
  1. Muresu Ibba GM, Poeta A, De Lorenzi G, Pupillo G, D'Annunzio G, Pezzarossi A, Bisceglia I, Mangone L. Melanoma in horses: distribution by sex, age, nationality, and slaughterhouse findings in 28 horses from Northern Italy. Vet Res Commun 2025 Oct 29;50(1):12.
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