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 - Funding Information:
This project was sponsored by the Bladder Cancer Advocacy Network (BCAN) through generous donations from the James Family Foundation, The JPB Foundation, and The Gerald C. McNamara and Renee K. Petrofes Charitable Fund. The sponsoring entity, BCAN, was involved in the study conception, planning, and manuscript review. The authors thank the Hoosier Cancer Research Network (HCRN) for their work compiling the data and specimens, the UNC Office of Genomic Research and cBioPortal for facilitating the sharing of genomic and clinical data, the UNC Pathology Services Core for help with the immune phenotyping and Caris Life Science for assistance compiling the genomic data. The authors would also like to acknowledge all of the patients and their families who participated in the UC-GENOME study. Additional funding was provided through the Cancer Center Core Support Grant (P30-CA016086) and R01-CA241810 (W.Y.K. and B.G.V.).
Funding Information:
UC-GENOME (ClinicalTrials.gov identifier: NCT02643043) was supported by the Bladder Cancer Advocacy Network (BCAN) and conducted at University of North Carolina at Chapel Hill, Fox Chase Cancer Center, Icahn School of Medicine at Mount Sinai, University of Washington/ Fred Hutchinson Cancer Research Center, Johns Hopkins University, University of Chicago, Memorial Sloan Kettering Cancer Center, and University of Southern California. The study was coordinated by the Hoosier Cancer Research Network (HCRN). The protocol was approved by all of the participating institutional review boards: University of North Carolina Institutional Review Board, Fox Chase Cancer Center Institutional Review Board, Icahn School of Medicine at Mount Sinai Institutional Review Board, Fred Hutch Institutional Review Board, Johns Hopkins Medicine Institutional Review Board, University of Chicago Institutional Review Board, Memorial Sloan Kettering Institutional Review Board, and USC Health Sciences Campus Institutional Review Board. All patients provided written informed consent. The study protocol is available as part of the Source Data file.
Funding Information:
This project was sponsored by the Bladder Cancer Advocacy Network (BCAN) through generous donations from the James Family Foundation, The JPB Foundation, and The Gerald C. McNamara and Renee K. Petrofes Charitable Fund. The sponsoring entity, BCAN, was involved in the study conception, planning, and manuscript review. The authors thank the Hoosier Cancer Research Network (HCRN) for their work compiling the data and specimens, the UNC Office of Genomic Research and cBioPortal for facilitating the sharing of genomic and clinical data, the UNC Pathology Services Core for help with the immune phenotyping and Caris Life Science for assistance compiling the genomic data. The authors would also like to acknowledge all of the patients and their families who participated in the UC-GENOME study. Additional funding was provided through the Cancer Center Core Support Grant (P30-CA016086) and R01-CA241810 (W.Y.K. and B.G.V.).
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.
UR - http://www.scopus.com/inward/record.url?scp=85141440042&partnerID=8YFLogxK
U2 - 10.1038/s41467-022-33980-9
DO - 10.1038/s41467-022-33980-9
M3 - Article
C2 - 36333289
AN - SCOPUS:85141440042
VL - 13
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 6658
ER -