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

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. Vincent, Diane Zipursky Quale, Sara E. Wobker, Katherine A. Hoadley, William Y. Kim, Matthew I. Milowsky

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number6658
JournalNature Communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022

Fingerprint

Dive into the research topics of 'Collaborative study from the Bladder Cancer Advocacy Network for the genomic analysis of metastatic urothelial cancer'. Together they form a unique fingerprint.

Cite this