Understanding_the_genetics_of_feline_urinary_bladder_TCC

Bladder cancer is the most common cancer of urinary system, with urothelial carcinoma (UC)/transitional cell carcinoma (TCC) accounting for 90% of the cases in Europe and USA. ~25% of patients have muscle invasive bladder cancer (MIBC), many of which either present with or later develop metastatic disease. With the contemporary chemotherapy regimens, the current 5-years survival rate is only 15%. Thus better treatments are needed. Bladder cancer in companion animals (cats and dogs) is usually UC/TCC. ~20% of dogs with bladder cancer have metastases at the time of diagnosis, and dogs with UC/TCC of the bladder only live for 6-12 months despite treatment. The epidemiological and histological similarities between UC/TCC in companion animals and humans, suggest they may be relevant models of the disease. Bladder cancer in cows is generally rare, however in parts of the world where cattle graze on bracken fern, tumours of the bladder are common (associated with chronic enzootic haematuria), due to the presence of the carcinogen ptaquiloside in the ferns. Given that exposure to chemicals is one of the risk factors for bladder cancer in humans, UC/TCC in cows may also represent a relevant model. We propose to whole-exome sequence tumor-germline pairs of primary (invasive/infiltrating) and metastatic urothelial/transitional cell carcinoma (UC/TCC) of the bladder from humans, as well as dogs, cats and cows. Our goal is to establish the mutational landscape of UC/TCC in these animals and to perform cross-species comparison with human bladder cancer. This will allow us to assess how genetically similar spontaneous UC/TCC in these animals is to the human disease and whether they represent relevant models. If so, it will help us to rationally apply emerging targeted therapies for UC/TCC across several species, in line with the One Health Initiative.