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Urinary Comprehensive Genomic Profiling Correlates Urothelial Carcinoma Mutations with Clinical Risk and Efficacy of Intervention

The clinical standard of care for urothelial carcinoma (UC) relies on invasive procedures with suboptimal performance. To enhance UC treatment, we developed a urinary comprehensive genomic profiling (uCGP) test, UroAmplitude, that measures mutations from tumor DNA present in urine. In this study, we...

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Autores principales: Bicocca, Vincent T., Phillips, Kevin G., Fischer, Daniel S., Caruso, Vincent M., Goudarzi, Mahdi, Garcia-Ransom, Monica, Lentz, Peter S., MacBride, Andrew R., Jensen, Brad W., Mazzarella, Brian C., Koppie, Theresa, Korkola, James E., Gray, Joe W., Levin, Trevor G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9571552/
https://www.ncbi.nlm.nih.gov/pubmed/36233691
http://dx.doi.org/10.3390/jcm11195827
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author Bicocca, Vincent T.
Phillips, Kevin G.
Fischer, Daniel S.
Caruso, Vincent M.
Goudarzi, Mahdi
Garcia-Ransom, Monica
Lentz, Peter S.
MacBride, Andrew R.
Jensen, Brad W.
Mazzarella, Brian C.
Koppie, Theresa
Korkola, James E.
Gray, Joe W.
Levin, Trevor G.
author_facet Bicocca, Vincent T.
Phillips, Kevin G.
Fischer, Daniel S.
Caruso, Vincent M.
Goudarzi, Mahdi
Garcia-Ransom, Monica
Lentz, Peter S.
MacBride, Andrew R.
Jensen, Brad W.
Mazzarella, Brian C.
Koppie, Theresa
Korkola, James E.
Gray, Joe W.
Levin, Trevor G.
author_sort Bicocca, Vincent T.
collection PubMed
description The clinical standard of care for urothelial carcinoma (UC) relies on invasive procedures with suboptimal performance. To enhance UC treatment, we developed a urinary comprehensive genomic profiling (uCGP) test, UroAmplitude, that measures mutations from tumor DNA present in urine. In this study, we performed a blinded, prospective validation of technical sensitivity and positive predictive value (PPV) using reference standards, and found at 1% allele frequency, mutation detection performs at 97.4% sensitivity and 80.4% PPV. We then prospectively compared the mutation profiles of urine-extracted DNA to those of matched tumor tissue to validate clinical performance. Here, we found tumor single-nucleotide variants were observed in the urine with a median concordance of 91.7% and uCGP revealed distinct patterns of genomic lesions enriched in low- and high-grade disease. Finally, we retrospectively explored longitudinal case studies to quantify residual disease following bladder-sparing treatments, and found uCGP detected residual disease in patients receiving bladder-sparing treatment and predicted recurrence and disease progression. These findings demonstrate the potential of the UroAmplitude platform to reliably identify and track mutations associated with UC at each stage of disease: diagnosis, treatment, and surveillance. Multiple case studies demonstrate utility for patient risk classification to guide both surgical and therapeutic interventions.
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spelling pubmed-95715522022-10-17 Urinary Comprehensive Genomic Profiling Correlates Urothelial Carcinoma Mutations with Clinical Risk and Efficacy of Intervention Bicocca, Vincent T. Phillips, Kevin G. Fischer, Daniel S. Caruso, Vincent M. Goudarzi, Mahdi Garcia-Ransom, Monica Lentz, Peter S. MacBride, Andrew R. Jensen, Brad W. Mazzarella, Brian C. Koppie, Theresa Korkola, James E. Gray, Joe W. Levin, Trevor G. J Clin Med Article The clinical standard of care for urothelial carcinoma (UC) relies on invasive procedures with suboptimal performance. To enhance UC treatment, we developed a urinary comprehensive genomic profiling (uCGP) test, UroAmplitude, that measures mutations from tumor DNA present in urine. In this study, we performed a blinded, prospective validation of technical sensitivity and positive predictive value (PPV) using reference standards, and found at 1% allele frequency, mutation detection performs at 97.4% sensitivity and 80.4% PPV. We then prospectively compared the mutation profiles of urine-extracted DNA to those of matched tumor tissue to validate clinical performance. Here, we found tumor single-nucleotide variants were observed in the urine with a median concordance of 91.7% and uCGP revealed distinct patterns of genomic lesions enriched in low- and high-grade disease. Finally, we retrospectively explored longitudinal case studies to quantify residual disease following bladder-sparing treatments, and found uCGP detected residual disease in patients receiving bladder-sparing treatment and predicted recurrence and disease progression. These findings demonstrate the potential of the UroAmplitude platform to reliably identify and track mutations associated with UC at each stage of disease: diagnosis, treatment, and surveillance. Multiple case studies demonstrate utility for patient risk classification to guide both surgical and therapeutic interventions. MDPI 2022-09-30 /pmc/articles/PMC9571552/ /pubmed/36233691 http://dx.doi.org/10.3390/jcm11195827 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bicocca, Vincent T.
Phillips, Kevin G.
Fischer, Daniel S.
Caruso, Vincent M.
Goudarzi, Mahdi
Garcia-Ransom, Monica
Lentz, Peter S.
MacBride, Andrew R.
Jensen, Brad W.
Mazzarella, Brian C.
Koppie, Theresa
Korkola, James E.
Gray, Joe W.
Levin, Trevor G.
Urinary Comprehensive Genomic Profiling Correlates Urothelial Carcinoma Mutations with Clinical Risk and Efficacy of Intervention
title Urinary Comprehensive Genomic Profiling Correlates Urothelial Carcinoma Mutations with Clinical Risk and Efficacy of Intervention
title_full Urinary Comprehensive Genomic Profiling Correlates Urothelial Carcinoma Mutations with Clinical Risk and Efficacy of Intervention
title_fullStr Urinary Comprehensive Genomic Profiling Correlates Urothelial Carcinoma Mutations with Clinical Risk and Efficacy of Intervention
title_full_unstemmed Urinary Comprehensive Genomic Profiling Correlates Urothelial Carcinoma Mutations with Clinical Risk and Efficacy of Intervention
title_short Urinary Comprehensive Genomic Profiling Correlates Urothelial Carcinoma Mutations with Clinical Risk and Efficacy of Intervention
title_sort urinary comprehensive genomic profiling correlates urothelial carcinoma mutations with clinical risk and efficacy of intervention
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9571552/
https://www.ncbi.nlm.nih.gov/pubmed/36233691
http://dx.doi.org/10.3390/jcm11195827
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