Sebastian Stasik1, Karsten Salomo2, Ulrike Heberling2, Michael Froehner2, Ulrich Sommer3, Gustavo B Baretton4, Gerhard Ehninger5, Manfred P Wirth6, Christian Thiede5, Susanne Fuessel7. 1. Medical Department I, University Hospital and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany; National Center for Tumor Diseases (NCT), Partner site Dresden, Dresden, Germany. 2. Department of Urology, University Hospital and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany. 3. Institute of Pathology, University Hospital and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany; National Center for Tumor Diseases (NCT), Partner site Dresden, Dresden, Germany. 4. Institute of Pathology, University Hospital and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany; National Center for Tumor Diseases (NCT), Partner site Dresden, Dresden, Germany; Tumor and normal tissue bank of Universitäts KrebsCentrum (UCC), University Hospital and Faculty of Medicine, Technische Universität Dresden, Germany; German Cancer Consortium (DKTK), Dresden, Germany. 5. Medical Department I, University Hospital and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany; National Center for Tumor Diseases (NCT), Partner site Dresden, Dresden, Germany; German Cancer Consortium (DKTK), Dresden, Germany. 6. Department of Urology, University Hospital and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany; National Center for Tumor Diseases (NCT), Partner site Dresden, Dresden, Germany; German Cancer Consortium (DKTK), Dresden, Germany. 7. Department of Urology, University Hospital and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany; National Center for Tumor Diseases (NCT), Partner site Dresden, Dresden, Germany. Electronic address: susanne.fuessel@uniklinikum-dresden.de.
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.
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.
Authors: Aadel A Chaudhuri; Bruna Pellini; Nadja Pejovic; Pradeep S Chauhan; Peter K Harris; Jeffrey J Szymanski; Zachary L Smith; Vivek K Arora Journal: JCO Precis Oncol Date: 2020-07-15
Authors: Douglas G Ward; Naheema S Gordon; Rebecca H Boucher; Sarah J Pirrie; Laura Baxter; Sascha Ott; Lee Silcock; Celina M Whalley; Joanne D Stockton; Andrew D Beggs; Mike Griffiths; Ben Abbotts; Hanieh Ijakipour; Fathimath N Latheef; Robert A Robinson; Andrew J White; Nicholas D James; Maurice P Zeegers; K K Cheng; Richard T Bryan Journal: BJU Int Date: 2019-06-19 Impact factor: 5.588
Authors: Maria Zvereva; Eduard Pisarev; Ismail Hosen; Olga Kisil; Simon Matskeplishvili; Elena Kubareva; David Kamalov; Alexander Tivtikyan; Arnaud Manel; Emmanuel Vian; Armais Kamalov; Thorsten Ecke; Florence Le Calvez-Kelm Journal: Int J Mol Sci Date: 2020-08-21 Impact factor: 5.923
Authors: Anouk E Hentschel; Emma E van der Toom; André N Vis; Johannes C F Ket; Judith Bosschieter; Martijn W Heymans; R Jeroen A van Moorselaar; Renske D M Steenbergen; Jakko A Nieuwenhuijzen Journal: BJU Int Date: 2020-08-16 Impact factor: 5.588