Genome Biology (Aug 2023)
Cross-species oncogenomics offers insight into human muscle-invasive bladder cancer
- Kim Wong,
- 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
Affiliations
- Kim Wong
- Experimental Cancer Genetics, Wellcome Sanger Institute, Wellcome Genome Campus
- Federico Abascal
- Experimental Cancer Genetics, Wellcome Sanger Institute, Wellcome Genome Campus
- Latasha Ludwig
- Department of Pathobiology, University of Guelph
- Heike Aupperle-Lellbach
- Laboklin GmbH & Co. KG, Bad Kissingen, Germany and Institute of Pathology, Department Comparative Experimental Pathology, School of Medicine, Technical University of Munich
- Julia Grassinger
- Laboklin GmbH & Co. KG, Bad Kissingen, Germany and Institute of Pathology, Department Comparative Experimental Pathology, School of Medicine, Technical University of Munich
- Colin W. Wright
- School of Pharmacy and Medical Sciences, University of Bradford
- Simon J. Allison
- Department of Pharmacy, University of Huddersfield
- Emma Pinder
- Department of Pharmacy, University of Huddersfield
- Roger M. Phillips
- Department of Pharmacy, University of Huddersfield
- Laura P. Romero
- Departmento de Patología, Facultad de Medicina Veterinaria Y Zootecnia, Universidad Nacional Autónoma de México (UNAM), CDMX
- Arnon Gal
- Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois at Urbana-Champaign
- Patrick J. Roady
- Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois at Urbana-Champaign
- Isabel Pires
- Department of Veterinary Science, CECAV-Veterinary and Animal Research Center, University of Trás-Os-Montes and Alto Douro
- Franco Guscetti
- Institute of Veterinary Pathology, University of Zurich
- John S. Munday
- School of Veterinary Science, Massey University
- Maria C. Peleteiro
- Faculty of Veterinary Medicine, Centre for Interdisciplinary Research in Animal Health (CIISA), University of Lisbon
- Carlos A. Pinto
- Faculty of Veterinary Medicine, Centre for Interdisciplinary Research in Animal Health (CIISA), University of Lisbon
- Tânia Carvalho
- Champalimaud Foundation
- João Cota
- Faculty of Veterinary Medicine, Centre for Interdisciplinary Research in Animal Health (CIISA), University of Lisbon
- Elizabeth C. Du Plessis
- Division of Pathology, IDEXX Laboratories
- Fernando Constantino-Casas
- Department of Veterinary Medicine, University of Cambridge
- Stephanie Plog
- The Veterinary Pathology Group (VPG)
- Lars Moe
- Department of Companion Animal Clinical Sciences, Norwegian University of Life Sciences
- Simone de Brot
- Institute of Animal Pathology, COMPATH, University of Bern
- Ingrid Bemelmans
- Cerba Vet
- Renée Laufer Amorim
- Veterinary Clinic Department, School of Veterinary Medicine and Animal Science, São Paulo State University
- Smitha R. Georgy
- Department of Anatomic Pathology, Faculty of Veterinary and Agricultural Sciences, University of Melbourne
- Justina Prada
- Department of Veterinary Science, CECAV-Veterinary and Animal Research Center, University of Trás-Os-Montes and Alto Douro
- Jorge del Pozo
- Royal Dick School of Veterinary Sciences, University of Edinburgh
- Marianne Heimann
- Louisiane de Carvalho Nunes
- Departamento de Medicina Veterinária, Universidade Federal Do Espírito Santo
- Outi Simola
- Finnish Food Authority
- Paolo Pazzi
- Department of Companion Animal Clinical Studies, Faculty of Veterinary Science, University of Pretoria
- Johan Steyl
- Department of Paraclinical Sciences, Faculty of Veterinary Science, University of Pretoria
- Rodrigo Ubukata
- E+ Especialidades Veterinárias - Veterinary Oncology
- Peter Vajdovich
- Department of Clinical Pathology and Oncology, University of Veterinary Medicine Budapest
- Simon L. Priestnall
- Department of Pathobiology and Population Sciences, The Royal Veterinary College
- Alejandro Suárez-Bonnet
- Department of Pathobiology and Population Sciences, The Royal Veterinary College
- Franco Roperto
- Dipartimento Di Biologia, Università Degli Studi Di Napoli Federico II
- Francesca Millanta
- Department of Veterinary Sciences, University of Pisa
- Chiara Palmieri
- School of Veterinary Science, The University of Queensland
- Ana L. Ortiz
- School of Veterinary Medicine and Science, University of Nottingham
- Claudio S. L. Barros
- Faculdade de Medicina Veterinária E Zootecnia, Universidade Federal de Mato Grosso Do Sul
- Aldo Gava
- Pathology Laboratory of the Centro de Ciencias Agro-Veterinarias, Universidade Do Estado de Santa Catarina
- Minna E. Söderström
- Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki
- Marie O’Donnell
- Department of Pathology, Western General Hospital
- Robert Klopfleisch
- Institute of Veterinary Pathology, Freie Universität Berlin
- Andrea Manrique-Rincón
- Experimental Cancer Genetics, Wellcome Sanger Institute, Wellcome Genome Campus
- Inigo Martincorena
- Experimental Cancer Genetics, Wellcome Sanger Institute, Wellcome Genome Campus
- Ingrid Ferreira
- Experimental Cancer Genetics, Wellcome Sanger Institute, Wellcome Genome Campus
- Mark J. Arends
- University of Edinburgh Division of Pathology, Cancer Research UK Edinburgh Cancer Centre, Institute of Genetics & Cancer
- Geoffrey A. Wood
- Department of Pathobiology, University of Guelph
- David J. Adams
- Experimental Cancer Genetics, Wellcome Sanger Institute, Wellcome Genome Campus
- Louise van der Weyden
- Experimental Cancer Genetics, Wellcome Sanger Institute, Wellcome Genome Campus
- DOI
- https://doi.org/10.1186/s13059-023-03026-4
- Journal volume & issue
-
Vol. 24,
no. 1
pp. 1 – 29
Abstract
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.
Keywords
