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Collaborative study from the Bladder Cancer Advocacy Network for the genomic analysis of metastatic urothelial cancer

Author

Listed:
  • Jeffrey S. Damrauer

    (University of North Carolina)

  • Wolfgang Beckabir

    (University of North Carolina
    University of North Carolina)

  • Jeff Klomp

    (University of North Carolina
    University of North Carolina)

  • Mi Zhou

    (University of North Carolina)

  • Elizabeth R. Plimack

    (Fox Chase Cancer Center, Temple Health)

  • Matthew D. Galsky

    (Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai)

  • Petros Grivas

    (University of Washington
    Clinical Research Division, Fred Hutchinson Cancer Center)

  • Noah M. Hahn

    (Johns Hopkins University School of Medicine)

  • Peter H. O’Donnell

    (University of Chicago)

  • Gopa Iyer

    (Memorial Sloan Kettering Cancer Center)

  • David I. Quinn

    (University of Southern California Norris Comprehensive Cancer Center)

  • Benjamin G. Vincent

    (University of North Carolina
    University of North Carolina
    University of North Carolina
    University of North Carolina)

  • Diane Zipursky Quale

    (Bladder Cancer Advocacy Network)

  • Sara E. Wobker

    (University of North Carolina
    University of North Carolina)

  • Katherine A. Hoadley

    (University of North Carolina
    University of North Carolina)

  • William Y. Kim

    (University of North Carolina
    University of North Carolina
    University of North Carolina
    University of North Carolina)

  • Matthew I. Milowsky

    (University of North Carolina
    University of North Carolina
    University of North Carolina)

Abstract

Urothelial Cancer - Genomic Analysis to Improve Patient Outcomes and Research (NCT02643043), UC-GENOME, is a genomic analysis and biospecimen repository study in 218 patients with metastatic urothelial carcinoma. Here we report on the primary outcome of the UC-GENOME—the proportion of subjects who received next generation sequencing (NGS) with treatment options—and present the initial genomic analyses and clinical correlates. 69.3% of subjects had potential treatment options, however only 5.0% received therapy based on NGS. We found an increased frequency of TP53E285K mutations as compared to non-metastatic cohorts and identified features associated with benefit to chemotherapy and immune checkpoint inhibition, including: Ba/Sq and Stroma-rich subtypes, APOBEC mutational signature (SBS13), and inflamed tumor immune phenotype. Finally, we derive a computational model incorporating both genomic and clinical features predictive of immune checkpoint inhibitor response. Future work will utilize the biospecimens alongside these foundational analyses toward a better understanding of urothelial carcinoma biology.

Suggested Citation

  • Jeffrey S. Damrauer & Wolfgang Beckabir & Jeff Klomp & Mi Zhou & Elizabeth R. Plimack & Matthew D. Galsky & Petros Grivas & Noah M. Hahn & Peter H. O’Donnell & Gopa Iyer & David I. Quinn & Benjamin G., 2022. "Collaborative study from the Bladder Cancer Advocacy Network for the genomic analysis of metastatic urothelial cancer," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33980-9
    DOI: 10.1038/s41467-022-33980-9
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    References listed on IDEAS

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    Cited by:

    1. Wolfgang Beckabir & Mi Zhou & Jin Seok Lee & Steven P. Vensko & Mark G. Woodcock & Hsing-Hui Wang & Sara E. Wobker & Gatphan Atassi & Alec D. Wilkinson & Kenneth Fowler & Leah M. Flick & Jeffrey S. Da, 2024. "Immune features are associated with response to neoadjuvant chemo-immunotherapy for muscle-invasive bladder cancer," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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