Evaluation of TERT promoter mutations in urinary cell-free DNA and sediment DNA for detection of bladder cancer.
Biomarkers, Tumor
/ genetics
Case-Control Studies
Cell-Free Nucleic Acids
/ genetics
Cell-Free System
DNA, Neoplasm
/ genetics
Feasibility Studies
Gene Frequency
High-Throughput Nucleotide Sequencing
Humans
Mutation
Promoter Regions, Genetic
Sensitivity and Specificity
Telomerase
/ genetics
Urinary Bladder Neoplasms
/ diagnosis
Bladder cancer
Cell-free DNA
Next generation sequencing
Non-invasive detection
TERT promoter mutation
Journal
Clinical biochemistry
ISSN: 1873-2933
Titre abrégé: Clin Biochem
Pays: United States
ID NLM: 0133660
Informations de publication
Date de publication:
Feb 2019
Feb 2019
Historique:
received:
31
08
2018
revised:
12
11
2018
accepted:
26
11
2018
pubmed:
12
12
2018
medline:
16
3
2019
entrez:
12
12
2018
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
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.
Identifiants
pubmed: 30528938
pii: S0009-9120(18)30948-2
doi: 10.1016/j.clinbiochem.2018.11.009
pii:
doi:
Substances chimiques
Biomarkers, Tumor
0
Cell-Free Nucleic Acids
0
DNA, Neoplasm
0
TERT protein, human
EC 2.7.7.49
Telomerase
EC 2.7.7.49
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
60-63Informations de copyright
Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.