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Updated: Jun 21, 2026
07:48
An Orthotopic Bladder Cancer Model for Gene Delivery Studies
Published on: December 1, 2013
12.4K
Comprehensive genomic characterization of early-stage bladder cancer
Frederik Prip1,2, Philippe Lamy1, Sia Viborg Lindskrog1,2
1Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
Nature Genetics
|January 3, 2025
Summary
Genomic analysis reveals significant variations in nonmuscle-invasive bladder cancer (NMIBC), with whole-genome doubling linked to poorer outcomes. Understanding these molecular differences is key for better patient risk assessment and treatment strategies.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Nonmuscle-invasive bladder cancer (NMIBC) requires improved risk stratification and treatment.
- Comprehensive molecular profiling is essential for understanding NMIBC heterogeneity.
Purpose of the Study:
- To comprehensively analyze the molecular landscape of NMIBC.
- To correlate genomic variations with clinical outcomes and molecular subtypes.
- To identify key drivers of disease aggressiveness in NMIBC.
Main Methods:
- Whole-exome sequencing (n=438), shallow whole-genome sequencing (n=362), and total RNA sequencing (n=414) were performed.
- Integrative clustering of multi-omics data was utilized.
- Genomic alterations, including loss of heterozygosity and whole-genome doubling (WGD), were analyzed.
Main Results:
- Significant genomic variation was observed in NMIBC, correlating with molecular subtypes.
- Frequent loss of heterozygosity in FGFR3 and 17p (TP53) was noted.
- Whole-genome doubling (WGD) occurred in 15% of tumors, associated with genomic instability, cell-cycle gene alterations, altered immune composition, and worse outcomes.
Conclusions:
- Genomic instability and immune cell exhaustion are critical factors in NMIBC aggressiveness.
- Multi-omics analysis provides insights into NMIBC molecular subtypes and progression.
- Findings support improved patient stratification for NMIBC based on molecular characteristics.
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