Publikationsdatenbank

Cross-species oncogenomics offers insight into human muscle-invasive bladder cancer (2023)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

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, R (WE 12)

Manrique-Rincón, Andrea

Martincorena, Inigo

Ferreira, Ingrid

Arends, Mark J.

Wood, Geoffrey A.

Adams, David J.

van der Weyden, Louise

Quelle

Genome Biology : biology for the post-genomic era

Bandzählung: 24

Heftzählung: 1

Seiten: Artikel 191

ISSN: 1474-760x

Sprache

Englisch

Verweise

URL (Volltext): https://genomebiology.biomedcentral.com/articles/10.1186/s13059-023-03026-4

DOI: 10.1186/s13059-023-03026-4

Pubmed: 37635261

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.