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Highly Sensitive and Specific Detection of Bladder Cancer via Targeted Ultra-deep Sequencing of Urinary DNA.
- Source :
-
European urology oncology [Eur Urol Oncol] 2023 Feb; Vol. 6 (1), pp. 67-75. Date of Electronic Publication: 2022 Apr 08. - Publication Year :
- 2023
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Abstract
- Background: There is an unmet need for an accurate, validated, noninvasive test for diagnosing and monitoring bladder cancer (BC). Detection of BC-associated mutations in urinary DNA via targeted deep sequencing could meet this need.<br />Objective: To test the ability of mutational analysis of urinary DNA to noninvasively detect BC within the context of haematuria investigations and non-muscle-invasive BC (NMIBC) surveillance.<br />Design, Setting, and Participants: Capture-based ultra-deep sequencing was performed for 443 somatic mutations in 23 genes in 591 urine cell-pellet DNAs from haematuria clinic patients and 293 from NMIBC surveillance patients. Variant calling was optimised to minimise false positives using urine samples from 162 haematuria clinic patients without BC.<br />Outcome Measurements and Statistical Analysis: The sensitivity and specificity for BC diagnosis were determined.<br />Results and Limitations: Mutational analysis of urinary DNA detected 144 of the 165 haematuria patients diagnosed with incident BC from two independent cohorts, yielding overall sensitivity of 87.3% (95% confidence interval [CI] 81.2-92.0%) at specificity of 84.8% (95% CI 79.9-89.0%). The sensitivity was 97.4% for grade 3, 86.5% for grade 2, and 70.8% for grade 1 BC. Among NMIBC surveillance patients, 25 out of 29 recurrent BCs were detected, yielding sensitivity of 86.2% (95% CI 70.8-97.7%) at specificity of 62.5% (95% CI 56.1-68.0%); a positive urine mutation test in the absence of clinically detectable disease was associated with a 2.6-fold increase in the risk of future recurrence. The low number of recurrences in the NMIBC surveillance cohort and the lower sensitivity for detecting grade 1 pTa BC are limitations.<br />Conclusions: Detection of mutations in a small panel of BC-associated genes could facilitate noninvasive BC testing and expedite haematuria investigations. Following further validation, the test could also play a role in NMIBC surveillance.<br />Patient Summary: Identification of alterations in genes that are frequently mutated in bladder cancer appears to be a promising strategy for detecting disease from urine samples and reducing reliance on examination of the bladder via a telescopic camera inserted through the urethra.<br /> (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 2588-9311
- Volume :
- 6
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- European urology oncology
- Publication Type :
- Academic Journal
- Accession number :
- 35410825
- Full Text :
- https://doi.org/10.1016/j.euo.2022.03.005