Highly Sensitive and Specific Detection of Bladder Cancer via Targeted Ultra-deep Sequencing of Urinary DNA

• DOI: 10.1016/j.euo.2022.03.005
• Publication Date: 2022-04-08T22:18:02Z
• Authors: Douglas G. Ward; Laura Baxter; Sascha Ott; Naheema S. Gordon; Junhui Wang; Prashant Patel; Kim Piechocki; Lee Silcock; Chris Sale; Maurice P. Zeegers; K.K. Cheng; Nicholas D. James; Richard T. Bryan
• Keywords: WJ Urogenital system. Urology; QZ Pathology. Oncology; Urinary Bladder; 610; High-Throughput Nucleotide Sequencing; DNA; 6. Clean water; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Urinary Bladder Neoplasms; 616; Humans; Hematuria

There is an unmet need for accurate, validated, noninvasive test diagnosing and monitoring bladder cancer (BC). Detection of BC-associated mutations in urinary DNA via targeted deep sequencing could meet this need. To the ability mutational analysis to noninvasively detect BC within context haematuria investigations non–muscle-invasive (NMIBC) surveillance. Capture-based ultra-deep was performed 443 somatic 23 genes 591 urine cell-pellet DNAs from clinic patients 293 NMIBC surveillance patients. Variant calling optimised minimise false positives using samples 162 without BC. The sensitivity specificity diagnosis were determined. Mutational detected 144 165 diagnosed with incident two independent cohorts, yielding overall 87.3% (95% confidence interval [CI] 81.2–92.0%) at 84.8% CI 79.9–89.0%). 97.4% grade 3, 86.5% 2, 70.8% 1 Among patients, 25 out 29 recurrent BCs detected, 86.2% 70.8–97.7%) 62.5% 56.1–68.0%); a positive mutation absence clinically detectable disease associated 2.6-fold increase risk future recurrence. low number recurrences cohort lower detecting pTa are limitations. small panel facilitate testing expedite investigations. Following further validation, also play role Identification alterations that frequently mutated appears be promising strategy reducing reliance on examination telescopic camera inserted through urethra.