1. Evaluation of TERT promoter mutations in urinary cell-free DNA and sediment DNA for detection of bladder cancer.
- Author
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Stasik S, Salomo K, Heberling U, Froehner M, Sommer U, Baretton GB, Ehninger G, Wirth MP, Thiede C, and Fuessel S
- Subjects
- Biomarkers, Tumor genetics, Biomarkers, Tumor urine, Case-Control Studies, Cell-Free System, DNA, Neoplasm genetics, Feasibility Studies, Gene Frequency, High-Throughput Nucleotide Sequencing, Humans, Sensitivity and Specificity, Cell-Free Nucleic Acids genetics, Cell-Free Nucleic Acids urine, DNA, Neoplasm urine, Mutation, Promoter Regions, Genetic, Telomerase genetics, Urinary Bladder Neoplasms diagnosis, Urinary Bladder Neoplasms genetics
- Abstract
Background: Cell-free DNA (cfDNA) is proposed to be a valuable source of biomarkers in liquid biopsies for various diseases as it is supposed to partially originate from tumor cells. However, data about the diagnostic implications of cfDNA in urine for the detection of bladder cancer (BCa) is sparse., Methods: We evaluated the usability of urinary cfDNA for diagnostic purposes compared to urine sediment DNA (sDNA) in 53 BCa patients and 36 control subjects by analyzing two abundant point-mutations (C228T/C250T) in the TERT promoter using Next-Generation Sequencing., Results: Mutations were detected in 77% of the urinary sDNA compared to 63% of the cfDNA samples. Moreover, the TERT mutation allele frequencies (MAF) were highly correlated in cfDNA and sDNA. In comparison, the accuracy of the TERT assay was higher in sDNA (84%) compared to cfDNA or voided urine cytology (both 77%). Interestingly, MAFs from leukocyte-rich urines were higher in cfDNA than in sDNA, indicating a diagnostic advantage of cfDNA in such urines., Conclusions: Urine-based mutation detection has the ability to augment and surpass voided urine cytology as the current gold-standard for the non-invasive detection and surveillance of BCa. The analysis of cell-free DNA provides no general diagnostic advantage compared to urine sediment DNA., (Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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