Transcriptomic & Genetic Profiling of Canine Oral Melanoma to Understand Metastasis

Presentation Description / Summary: Canine oral melanoma (cOM) is the most common oral tumour in dogs. cOM is a devastating diagnosis, characterised by local invasion, recurrence after radical surgical resection, rapid progression to advanced-stage disease, and limited response to chemotherapy and/or radiation therapy. Almost all patients develop metastatic disease, and dogs diagnosed with cOM have a median survival of just 335 days. There is a desperate need to advance our understanding of cOM, which remains incredibly difficult to treat. The genetics and pathophysiology of cOM is incompletely understood which has confounded efforts to develop effective treatments. In human cancer, transcriptomic signature-based strategies have been successfully used early in the pharmaceutical pipeline to guide relationship hypotheses and candidate selection, predict efficacy of already approved drugs, and identify potentially toxic drug candidates. As a collaborative team of veterinary pathologists and senior researchers with experience in melanoma biology, sequencing, bioinformatics, and organoid development, we are performing genetic and transcriptomic sequencing of archived naturally-occurring cOM biosamples to identify cOM subtypes and determine the genetic changes that distinguish between primary, non-metastatic and metastatic cOM. In parallel, we are also sequencing human oral mucosal melanoma and their metastatic lesions to identify similarities and differences between the species. By working with naturally occurring cOMs which optimally model hMM, identification of novel anti-metastatic drugs and results from their trial in clinical canine patients will also have huge translational potentials for future drug trials in human patients with MM.

Learner Outcomes: Understand how to achieve RNA sequencing (RNAseq) and whole exam sequencing (WES) from formalin-fixed, paraffin-embedded samples Learn how RNAseq and WES of canine oral melanomas compares to human oral melanomas Discuss genetic signatures between primary and metastatic canine and human oral melanoma lesions