The risk of developing urothelial carcinoma of the bladder (UCB) in patients treated by radical nephroureterectomy (RNU) for an upper urinary tract urothelial carcinoma (UTUC) is 22-47% in the two years after surgery. Subject of debate remains whether UTUC and the subsequent UCB are clonally related or represent separate origins. To investigate the clonal relationship between both entities, we performed targeted DNA sequencing of a panel of 41 genes on matched normal and tumor tissue of 15 primary UTUC patients treated by RNU who later developed 19 UCBs. Based on the detected tumor-specific DNA aberrations, the paired UTUC and UCB(s) of 11 patients (73.3%) showed a clonal relation, whereas in four patients the molecular results did not indicate a clear clonal relationship. Our results support the hypothesis that UCBs following a primary surgically resected UTUC are predominantly clonally-derived recurrences and not separate entities. This article is protected by copyright. All rights reserved.
International journal of cancer. 2020 Oct 02 [Epub ahead of print]
Thomas van Doeveren, Jose A Nakauma-Gonzalez, Andrew S Mason, Geert J L H van Leenders, Tahlita C M Zuiverloon, Ellen C Zwarthoff, Isabelle C Meijssen, Angelique C van der Made, Antoine G van der Heijden, Kees Hendricksen, Bas W G van Rhijn, Charlotte S Voskuilen, Job van Riet, Winand N M Dinjens, Hendrikus J Dubbink, Harmen J G van de Werken, Joost L Boormans
Department of Urology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, the Netherlands., Jack Birch Unit for Molecular Carcinogenesis, Department of Biology, The University of York, York, UK., Department of Pathology, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, the Netherlands., Department of Urology, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, the Netherlands., Department of Urology, Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital, Amsterdam, The Netherlands.