Kim Wong
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.; Constantino-Casas, Fernando; Plog, Stephanie; Moe, Lars; de Brot, Simone; Bemelmans, Ingrid; Amorim, Renée Laufer; Georgy, Smitha R.; Prada, Justina; del Pozo, Jorge; Heimann, Marianne; de Carvalho Nunes, Louisiane; Simola, Outi; Pazzi, Paolo; Steyl, Johan; Ubukata, Rodrigo; Vajdovich, Peter; Priestnall, Simon L.; Suárez-Bonnet, Alejandro; Roperto, Franco; Millanta, Francesca; Palmieri, Chiara; Ortiz, Ana L.; Barros, Claudio S. L.; Gava, Aldo; Söderström, Minna E.; O’Donnell, Marie; Klopfleisch, Robert; Manrique-Rincón, Andrea; Martincorena, Inigo; Ferreira, Ingrid; Arends, Mark J.; Wood, Geoffrey A.; Adams, David J.; van der Weyden, Lo...
Authors
Federico Abascal
Latasha Ludwig
Heike Aupperle-Lellbach
Julia Grassinger
Colin W. Wright
Simon J. Allison
Emma Pinder
Roger M. Phillips
Laura P. Romero
Arnon Gal
Patrick J. Roady
Isabel Pires
Franco Guscetti
John S. Munday
Maria C. Peleteiro
Carlos A. Pinto
Tânia Carvalho
João Cota
Elizabeth C. Du Plessis
Fernando Constantino-Casas
Stephanie Plog
Lars Moe
Simone de Brot
Ingrid Bemelmans
Renée Laufer Amorim
Smitha R. Georgy
Justina Prada
Jorge del Pozo
Marianne Heimann
Louisiane de Carvalho Nunes
Outi Simola
Paolo Pazzi
Johan Steyl
Rodrigo Ubukata
Peter Vajdovich
Simon L. Priestnall
Alejandro Suárez-Bonnet
Franco Roperto
Francesca Millanta
Chiara Palmieri
Ana L. Ortiz
Claudio S. L. Barros
Aldo Gava
Minna E. Söderström
Marie O’Donnell
Robert Klopfleisch
Andrea Manrique-Rincón
Inigo Martincorena
Ingrid Ferreira
Mark J. Arends
Geoffrey A. Wood
David J. Adams
Louise van der Weyden
Abstract
Background: 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. Results: 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. Conclusion: 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.
Citation
Wong, K., Abascal, F., Ludwig, L., Aupperle-Lellbach, H., Grassinger, J., Wright, C. W., …van der Weyden, L. (2023). Cross-species oncogenomics offers insight into human muscle-invasive bladder cancer. Genome Biology, 24(1), Article 191. https://doi.org/10.1186/s13059-023-03026-4
Journal Article Type | Article |
---|---|
Acceptance Date | Jul 28, 2023 |
Online Publication Date | Aug 28, 2023 |
Publication Date | Aug 28, 2023 |
Deposit Date | Sep 4, 2023 |
Publicly Available Date | Sep 4, 2023 |
Journal | Genome Biology |
Print ISSN | 1474-760X |
Electronic ISSN | 1465-6906 |
Publisher | Springer Verlag |
Peer Reviewed | Peer Reviewed |
Volume | 24 |
Issue | 1 |
Article Number | 191 |
DOI | https://doi.org/10.1186/s13059-023-03026-4 |
Keywords | Canine, Pteridium aquilinum, Bovine, Bracken, Mutational signature, Cross-species comparison, Feline, Urinary bladder, Cancer, Ptaquiloside |
Public URL | https://nottingham-repository.worktribe.com/output/24866375 |
Publisher URL | https://genomebiology.biomedcentral.com/articles/10.1186/s13059-023-03026-4 |
Additional Information | Received: 2 December 2022; Accepted: 28 July 2023; First Online: 28 August 2023; : ; : The Research Governance team at the Wellcome Sanger Institute approved this study and ensured it complied with the Access and Benefit Sharing regulations globally, the Nagoya Protocol and UK regulations. All tissue samples were sent from veterinary pathologists that confirmed they were collected from animals with the owner’s consent, and the sampling was performed for diagnostic purposes with the primary aim of benefiting the animal. If the samples were taken post-mortem, the animal was euthanized for purposes relating to its welfare; in the case of the cows, they were sacrificed using a captive bolt that was performed by a veterinarian at an officially registered/regulated abattoir or veterinary center.; : Not applicable.; : The authors declare no competing or financial interests. |
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