Bracken_fern_mutational_signature_Dupseq_WGS

Bladder cancer is the most common cancer of urinary system, with urothelial carcinoma (UC) 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, and an important aspect of therapy development is animal models. Bladder cancer in cows is generally rare, however in parts of the world where cattle graze on bracken fern (BF), tumours of the bladder are common, due to the presence of the carcinogen ptaquiloside (PTA) in the ferns. Given that exposure to chemicals is one of the risk factors for bladder cancer in humans, UC in cows may represent a relevant model. We sequenced UC samples from cows that grazed on BF and identified a mutational signature. To verify that the signature we are seeing is due to the presence of the PTA in the BF, we have cultured a human bladder cancer cell line with PTA (at IC20 and IC50) aor vehicle and collected samples at 4 different timepoints (d3, d7, d10, d14).