Oronasal mucosal melanoma is defined by two transcriptional subtypes in humans and dogs with implications for diagnosis and therapy
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| Natura: | Artículo Open Access |
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Wiley
2025
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| author | Kelly L Bowlt Blacklock Kevin Donnelly Yuting Lu Jorge del Pozo Laura Glendinning Gerry Polton Laura Selmic Jean‐Benoit Tanis David Killick Maciej Parys Joanna S Morris Inge Breathnach Stefano Zago Sara M Gould Darren J Shaw Michael S Tivers Davide Malucelli Ana Marques Katarzyna Purzycka Matteo Cantatore Marie E Mathers Mark Stares Alison Meynert E Elizabeth Patton |
| author_facet | Kelly L Bowlt Blacklock Kevin Donnelly Yuting Lu Jorge del Pozo Laura Glendinning Gerry Polton Laura Selmic Jean‐Benoit Tanis David Killick Maciej Parys Joanna S Morris Inge Breathnach Stefano Zago Sara M Gould Darren J Shaw Michael S Tivers Davide Malucelli Ana Marques Katarzyna Purzycka Matteo Cantatore Marie E Mathers Mark Stares Alison Meynert E Elizabeth Patton Kelly L Bowlt Blacklock Kevin Donnelly Yuting Lu Jorge del Pozo Laura Glendinning Gerry Polton Laura Selmic Jean‐Benoit Tanis David Killick Maciej Parys Joanna S Morris Inge Breathnach Stefano Zago Sara M Gould Darren J Shaw Michael S Tivers Davide Malucelli Ana Marques Katarzyna Purzycka Matteo Cantatore Marie E Mathers Mark Stares Alison Meynert E Elizabeth Patton |
| collection | Wiley Open Access |
| contents | Oronasal mucosal melanoma is defined by two transcriptional subtypes in humans and dogs with implications for diagnosis and therapy Kelly L Bowlt Blacklock Kevin Donnelly Yuting Lu Jorge del Pozo Laura Glendinning Gerry Polton Laura Selmic Jean‐Benoit Tanis David Killick Maciej Parys Joanna S Morris Inge Breathnach Stefano Zago Sara M Gould Darren J Shaw Michael S Tivers Davide Malucelli Ana Marques Katarzyna Purzycka Matteo Cantatore Marie E Mathers Mark Stares Alison Meynert E Elizabeth Patton The Journal of Pathology Abstract Mucosal melanoma is a rare melanoma subtype associated with a poor prognosis and limited existing therapeutic interventions, in part due to a lack of actionable targets and translational animal models for preclinical trials. Comprehensive data on this tumour type are scarce, and existing data often overlooks the importance of the anatomical site of origin. We evaluated human and canine oronasal mucosal melanoma (OMM) to determine whether the common canine disease could inform the rare human equivalent. Using a human and canine primary OMM cohort of treatment‐naive archival tissue, alongside clinicopathological data, we obtained transcriptomic, immunohistochemical, and microbiome data from both species. We defined the transcriptomic landscape in both species and linked our findings to immunohistochemical, microbiome, and clinical data. Human and dog OMM stratified into two distinctive transcriptional groups, which we defined using a species‐independent 41‐gene signature. These two subgroups are termed CTLA4‐high and MET‐high and indicate actionable targets for OMM patients. To guide clinical decision‐making, we developed immunohistochemical diagnostic tools that distinguish between transcriptomic subgroups. We found that OMM had conserved transcriptomic subtypes and biological similarity between human and canine OMM, with significant implications for patient classification, treatment, and clinical trial design. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. 10.1002/path.6377 http://creativecommons.org/licenses/by/4.0/ |
| doi_str_mv | 10.1002/path.6377 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_path_6377 |
| institution | Wiley Open Access |
| license_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| publishDate | 2025 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Oronasal mucosal melanoma is defined by two transcriptional subtypes in humans and dogs with implications for diagnosis and therapy Kelly L Bowlt Blacklock Kevin Donnelly Yuting Lu Jorge del Pozo Laura Glendinning Gerry Polton Laura Selmic Jean‐Benoit Tanis David Killick Maciej Parys Joanna S Morris Inge Breathnach Stefano Zago Sara M Gould Darren J Shaw Michael S Tivers Davide Malucelli Ana Marques Katarzyna Purzycka Matteo Cantatore Marie E Mathers Mark Stares Alison Meynert E Elizabeth Patton The Journal of Pathology Oronasal mucosal melanoma is defined by two transcriptional subtypes in humans and dogs with implications for diagnosis and therapy Kelly L Bowlt Blacklock Kevin Donnelly Yuting Lu Jorge del Pozo Laura Glendinning Gerry Polton Laura Selmic Jean‐Benoit Tanis David Killick Maciej Parys Joanna S Morris Inge Breathnach Stefano Zago Sara M Gould Darren J Shaw Michael S Tivers Davide Malucelli Ana Marques Katarzyna Purzycka Matteo Cantatore Marie E Mathers Mark Stares Alison Meynert E Elizabeth Patton The Journal of Pathology Abstract Mucosal melanoma is a rare melanoma subtype associated with a poor prognosis and limited existing therapeutic interventions, in part due to a lack of actionable targets and translational animal models for preclinical trials. Comprehensive data on this tumour type are scarce, and existing data often overlooks the importance of the anatomical site of origin. We evaluated human and canine oronasal mucosal melanoma (OMM) to determine whether the common canine disease could inform the rare human equivalent. Using a human and canine primary OMM cohort of treatment‐naive archival tissue, alongside clinicopathological data, we obtained transcriptomic, immunohistochemical, and microbiome data from both species. We defined the transcriptomic landscape in both species and linked our findings to immunohistochemical, microbiome, and clinical data. Human and dog OMM stratified into two distinctive transcriptional groups, which we defined using a species‐independent 41‐gene signature. These two subgroups are termed CTLA4‐high and MET‐high and indicate actionable targets for OMM patients. To guide clinical decision‐making, we developed immunohistochemical diagnostic tools that distinguish between transcriptomic subgroups. We found that OMM had conserved transcriptomic subtypes and biological similarity between human and canine OMM, with significant implications for patient classification, treatment, and clinical trial design. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. 10.1002/path.6377 http://creativecommons.org/licenses/by/4.0/ |
| title | Oronasal mucosal melanoma is defined by two transcriptional subtypes in humans and dogs with implications for diagnosis and therapy |
| topic | The Journal of Pathology |
| url | https://pathsocjournals.onlinelibrary.wiley.com/doi/10.1002/path.6377 |