Comprehensive genomic characterization of early-stage bladder cancer

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• dc.contributor.author Prip, Frederik
• dc.contributor.author Real, Francisco X.
• dc.contributor.author Dyrskjøt, Lars
• dc.date.accessioned 2025-02-21T07:15:31Z
• dc.date.available 2025-02-21T07:15:31Z
• dc.date.issued 2025
• dc.description.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.
• dc.format.mimetype application/pdf
• dc.identifier.citation Prip F, Lamy P, Lindskrog SV, Strandgaard T, Nordentoft I, Birkenkamp-Demtröder K, et al. Comprehensive genomic characterization of early-stage bladder cancer. Nat Genet. 2025 Jan;57(1):115-25. DOI: 10.1038/s41588-024-02030-z
• dc.identifier.doi http://dx.doi.org/10.1038/s41588-024-02030-z
• dc.identifier.issn 1061-4036
• dc.identifier.uri http://hdl.handle.net/10230/69671
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Nat Genet. 2025 Jan;57(1):115-25
• dc.rights © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
• dc.subject.keyword Bladder cancer
• dc.subject.keyword Tumour biomarkers
• dc.title Comprehensive genomic characterization of early-stage bladder cancer
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion