TY - JOUR
T1 - Collaborative study from the Bladder Cancer Advocacy Network for the genomic analysis of metastatic urothelial cancer
AU - Damrauer, Jeffrey S.
AU - Beckabir, Wolfgang
AU - Klomp, Jeff
AU - Zhou, Mi
AU - Plimack, Elizabeth R.
AU - Galsky, Matthew D.
AU - Grivas, Petros
AU - Hahn, Noah M.
AU - O’Donnell, Peter H.
AU - Iyer, Gopa
AU - Quinn, David I.
AU - Vincent, Benjamin G.
AU - Quale, Diane Zipursky
AU - Wobker, Sara E.
AU - Hoadley, Katherine A.
AU - Kim, William Y.
AU - Milowsky, Matthew I.
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-022-33980-9
DO - 10.1038/s41467-022-33980-9
M3 - Article
C2 - 36333289
AN - SCOPUS:85141440042
SN - 2041-1723
VL - 13
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 6658
ER -