GENOMICS: Gene Expression in Oral Melanoma for Integrated Cross-Species Stratification

Oronasal mucosal melanoma (OMM) is a highly aggressive cancer with poor survival outcomes, affecting both humans and dogs. Median survival is ~1 year in dogs and only ~15% of human patients survive 5 years. OMM’s high metastatic potential and limited therapeutic options underscore the need for innovative approaches.

Our research has identified two transcriptional subgroups of OMM: CTLA4-high (“immune hot”) tumors, potentially responsive to anti-CTLA4 therapy, and MET-high (“immune cold”) tumors, which may benefit from targeted treatments. These findings were derived from archival human and canine formalin-fixed paraffin-embedded (FFPE) tissue and clinical records. While immunohistochemical markers partially differentiate these subgroups, they lack diagnostic precision.

We have developed a species-independent 41-gene signature that accurately stratifies OMM into actionable subgroups, reflecting the biological similarity between human and canine disease. This project aims to refine and validate this gene signature assay to advance precision oncology in both species.

Project Objectives:

1. Refine the 41-gene assay for accurate OMM classification.
2. Validate its accuracy using archival FFPE samples and bulk RNA sequencing.
3. Assess its clinical utility in predicting therapeutic outcomes, particularly for anti-CTLA4 therapy in humans.
4. Establish a framework for cross-species clinical trials to explore OMM immunotherapy.

Impact: This project bridges human and veterinary oncology, fostering One Medicine collaboration. For humans, it offers personalized treatment strategies, optimizing immunotherapy and targeted therapies. For dogs, it facilitates innovative clinical trials, addressing unmet needs in veterinary care. The validated assay will revolutionize OMM management by enabling actionable insights across species, advancing both human and veterinary medicine.

Funding information and application procedures:

This 3.5 year studentship opportunity is open to UK and international students and provides funding to cover stipend, tuition fees and consumable/travel costs. 

Application form can be downloaded via https://vet.ed.ac.uk/sites/default/files/2024-12/R%28D%29SVS%20and%20Roslin%20Foundation%20PhD%20studentship%20application%20form_0.docx

Please send your completed Application Form to RDSVS.Studentship.Applications@ed.ac.uk

If you are applying for more than one studentship please submit a separate application with a closing date of noon on 13^th February 2025 at Studentships | The Royal (Dick) School of Veterinary Studies