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

Autor: Vincent T. Bicocca, Kevin G. Phillips, Daniel S. Fischer, Vincent M. Caruso, Mahdi Goudarzi, Monica Garcia-Ransom, Peter S. Lentz, Andrew R. MacBride, Brad W. Jensen, Brian C. Mazzarella, Theresa Koppie, James E. Korkola, Joe W. Gray, Trevor G. Levin
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Journal of Clinical Medicine, Vol 11, Iss 19, p 5827 (2022)
Druh dokumentu: article
ISSN: 11195827
2077-0383
DOI: 10.3390/jcm11195827
Popis: 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.
Databáze: Directory of Open Access Journals
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