D.A. Kayes, B.T. Blacklock, E. Scurrell, L. Murphy, K.L. Bowlt Blacklock

Feline diffuse iris melanoma (FDIM) is the most common ocular tumour of cats. Early lesions begin as iris pigmentation (melanosis) and undergo malignant transformation to FDIM. When neoplastic cells reach the scleral venous plexus, metastasis is highly likely. Enucleation is the treatment of choice but does not address metastatic disease. The genetics and pathophysiology of FDIM is incompletely understood, confounding 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. The objective of the study is to understand the molecular mechanisms that underlie FDIM initiation, local invasion, and metastatic progression.
Laser capture microdissection will be used to isolate iris melanoma, early FDIM and late FDIM lesions from formalin-fixed, paraffin-embedded tissue from feline patients who have underwent enucleation for reasons other than this study.
RNA-sequencing will be performed to i) identify transcriptional landscapes of iris melanosis, early FDIM, and late FDIM, and ii) determine transcriptional changes associated with tumour invasion and metastasis, and thereby identify biomarkers of invasion/metastasis and potential anti-cancer drug candidates. The genetic landscape of FDIM will be compared to datasets for human uveal melanoma (UM) to demonstrate whether FDIM is a reliable naturally occurring disease model for UM. In future, knowledge gained can be used to develop relevant cellular models for in-vitro trials of novel anti-cancer therapies identified during this study.