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International Journal of Clinical Oncology

Comparative genomic landscape of primary and metastatic bladder urothelial carcinoma in a large-scale cohort

Authors
Akira Ohtsu
Yusuke Otani
Seiji Arai
Anna Rogachevskaya
Vanessa D. Chin
Shinichi Toyooka
Kazuhiro Suzuki
Wenyi Wei
Atsushi Tanaka
Published in
International Journal of Clinical Oncology

Abstract

Background

Metastatic bladder urothelial carcinoma has poor survival, and large comparative genomic studies using uniform targeted sequencing of paired primary and metastatic lesions remain limited. We compared gene- and pathway-level alterations between primary and metastatic tumors

Methods

We analyzed 2,880 bladder urothelial carcinoma samples (2,305 primary; 575 metastatic) from 2,343 patients profiled with MSK-IMPACT. Somatic mutations and copy number alterations were integrated per gene and compared between primary and metastatic samples in the full cohort and in a paired subset using standard statistical tests.

Results

Primary and metastatic samples showed broadly similar driver landscapes. In the full cohort, KDM6A, FGFR3, STAG2, and ERCC2 were more frequently altered in primary tumors, whereas no individual genes were enriched in metastases; these differences were not significant in paired analyses. At the pathway level, TP53 pathway alterations were relatively more frequent in metastases, while DNA damage response alterations were enriched in primary tumors; other pathways showed comparable alteration rates. Apoptosis-focused analyses identified no significant gene-level differences, but suggested a trend toward higher alteration rates in the TP53 pathway and apoptosis regulators in metastases.

Conclusion

Primary and metastatic lesions of bladder urothelial carcinoma show broadly similar gene- and pathway-level alteration profiles on targeted DNA sequencing. TP53 pathway and apoptosis-related alterations are modestly more frequent in metastases, consistent with impaired stress responses and apoptosis evasion.
Title
Comparative genomic landscape of primary and metastatic bladder urothelial carcinoma in a large-scale cohort
Authors
Akira Ohtsu
Yusuke Otani
Seiji Arai
Anna Rogachevskaya
Vanessa D. Chin
Shinichi Toyooka
Kazuhiro Suzuki
Wenyi Wei
Atsushi Tanaka
Publication date
08-03-2026
Publisher
Springer Nature Singapore
Published in
International Journal of Clinical Oncology
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI
https://doi.org/10.1007/s10147-026-03005-2
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Case simulations: Biomarker-driven management of NSCLC (Link opens in a new window)

Do you want to assess your biomarker testing skills and management decisions? Use these simulation-based case studies based on realistic NSCLC scenarios to do so in a practical and secure environment.

Independent Medical Education Grant:
  • Bayer HealthCare Pharmaceuticals Inc.
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How-to guide for healthcare professionals: understanding genomic reports

This educational activity was initiated, funded and co-developed by Boehringer Ingelheim and is intended for healthcare professionals in the UK and Ireland only. 

Genomic testing helps inform cancer diagnosis, prognosis, and treatment. A genomic report is generated by the laboratory carrying out next-generation sequencing to analyze biopsy samples. Access this educational microsite to learn more about typical genomic report content and how to interpret test results for patients with cancer.

NP-GB-106631 | Jan 2026

Commissioned by:
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