Comprehensive genomic characterization of early-stage bladder cancer
Prip F, Lamy P, Lindskrog SV, Strandgaard T, Nordentoft I, Birkenkamp-Demtröder K, Birkbak NJ, Kristjánsdóttir N, Kjær A, Andreasen TG, Ahrenfeldt J, Pedersen JS, Rasmussen AM, Hermann GG, Mogensen K, Petersen AC, Hartmann A, Grimm MO, Horstmann M, Nawroth R, Segersten U, Sikic D, van Kessel KE, Zwarthoff EC, Maurer T, Simic T, Malmström PU, Malats N, Jensen JB, Real FX, Dyrskjøt L (2025)
Publication Type: Journal article
Publication year: 2025
Journal
Article Number: 2301
DOI: 10.1038/s41588-024-02030-z
Abstract
Understanding the molecular landscape of nonmuscle-invasive bladder cancer (NMIBC) is essential to improve risk assessment and treatment regimens. We performed a comprehensive genomic analysis of patients with NMIBC using whole-exome sequencing (n = 438), shallow whole-genome sequencing (n = 362) and total RNA sequencing (n = 414). A large genomic variation within NMIBC was observed and correlated with different molecular subtypes. Frequent loss of heterozygosity in FGFR3 and 17p (affecting TP53) was found in tumors with mutations in FGFR3 and TP53, respectively. Whole-genome doubling (WGD) was observed in 15% of the tumors and was associated with worse outcomes. Tumors with WGD were genomically unstable, with alterations in cell-cycle-related genes and an altered immune composition. Finally, integrative clustering of multi-omics data highlighted the important role of genomic instability and immune cell exhaustion in disease aggressiveness. These findings advance our understanding of genomic differences associated with disease aggressiveness in NMIBC and may ultimately improve patient stratification.
Authors with CRIS profile
Involved external institutions
Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO)
Spain (ES)
Aarhus University Hospital / Aarhus Universitetshospital
Denmark (DK)
Universitätsklinikum Jena
Germany (DE)
Universitätsklinikum Essen
Germany (DE)
Klinikum rechts der Isar
Germany (DE)
Erasmus University Medical Center (MC)
Netherlands (NL)
Universitätsklinikum Hamburg-Eppendorf (UKE)
Germany (DE)
University of Belgrade / Универзитет у Београду
Serbia (RS)
Uppsala University
Sweden (SE)
Aarhus University
Denmark (DK)
Gentofte Hospital
Denmark (DK)
Aalborg Universitetshospital
Denmark (DK)
Spain (ES)
Aarhus University Hospital / Aarhus Universitetshospital
Denmark (DK)
Universitätsklinikum Jena
Germany (DE)
Universitätsklinikum Essen
Germany (DE)
Klinikum rechts der Isar
Germany (DE)
Erasmus University Medical Center (MC)
Netherlands (NL)
Universitätsklinikum Hamburg-Eppendorf (UKE)
Germany (DE)
University of Belgrade / Универзитет у Београду
Serbia (RS)
Uppsala University
Sweden (SE)
Aarhus University
Denmark (DK)
Gentofte Hospital
Denmark (DK)
Aalborg Universitetshospital
Denmark (DK)
How to cite
APA:
Prip, F., Lamy, P., Lindskrog, S.V., Strandgaard, T., Nordentoft, I., Birkenkamp-Demtröder, K.,... Dyrskjøt, L. (2025). Comprehensive genomic characterization of early-stage bladder cancer. Nature Genetics. https://doi.org/10.1038/s41588-024-02030-z
MLA:
Prip, Frederik, et al. "Comprehensive genomic characterization of early-stage bladder cancer." Nature Genetics (2025).
BibTeX: Download