Cross-species oncogenomics offers insight into human muscle-invasive bladder cancer.

Wong, Kim; Abascal, Federico; Ludwig, Latasha; Aupperle-Lellbach, Heike; Grassinger, Julia; Wright, Colin W; Allison, Simon J; Pinder, Emma; Phillips, Roger M; Romero, Laura P; Gal, Arnon; Roady, Patrick J; Pires, Isabel; Guscetti, Franco; Munday, John S; Peleteiro, Maria C; Pinto, Carlos A; Carvalho, Tânia; Cota, João; Du Plessis, Elizabeth C; ... (2023). Cross-species oncogenomics offers insight into human muscle-invasive bladder cancer. Genome biology, 24(1), p. 191. BioMed Central Ltd. 10.1186/s13059-023-03026-4

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In humans, muscle-invasive bladder cancer (MIBC) is highly aggressive and associated with a poor prognosis. With a high mutation load and large number of altered genes, strategies to delineate key driver events are necessary. Dogs and cats develop urothelial carcinoma (UC) with histological and clinical similarities to human MIBC. Cattle that graze on bracken fern also develop UC, associated with exposure to the carcinogen ptaquiloside. These species may represent relevant animal models of spontaneous and carcinogen-induced UC that can provide insight into human MIBC.


Whole-exome sequencing of domestic canine (n = 87) and feline (n = 23) UC, and comparative analysis with human MIBC reveals a lower mutation rate in animal cases and the absence of APOBEC mutational signatures. A convergence of driver genes (ARID1A, KDM6A, TP53, FAT1, and NRAS) is discovered, along with common focally amplified and deleted genes involved in regulation of the cell cycle and chromatin remodelling. We identify mismatch repair deficiency in a subset of canine and feline UCs with biallelic inactivation of MSH2. Bovine UC (n = 8) is distinctly different; we identify novel mutational signatures which are recapitulated in vitro in human urinary bladder UC cells treated with bracken fern extracts or purified ptaquiloside.


Canine and feline urinary bladder UC represent relevant models of MIBC in humans, and cross-species analysis can identify evolutionarily conserved driver genes. We characterize mutational signatures in bovine UC associated with bracken fern and ptaquiloside exposure, a human-linked cancer exposure. Our work demonstrates the relevance of cross-species comparative analysis in understanding both human and animal UC.

Item Type:

Journal Article (Original Article)


05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)

UniBE Contributor:

De Brot, Simone Danielle


600 Technology > 630 Agriculture




BioMed Central Ltd.




Pubmed Import

Date Deposited:

28 Aug 2023 12:27

Last Modified:

29 Aug 2023 04:22

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

Bovine Bracken Cancer Canine Cross-species comparison Feline Mutational signature Ptaquiloside Pteridium aquilinum Urinary bladder




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