MP36-12 CLONALITY OF BLADDER TUMORS FOLLOWING RADICAL NEPHROURETERECTOMY – AGAINST THE FIELD DEFECT HYPOTHESIS

You have accessJournal of UrologyBladder Cancer: Basic Research I1 Apr 2015MP36-12 CLONALITY OF BLADDER TUMORS FOLLOWING RADICAL NEPHROURETERECTOMY – AGAINST THE FIELD DEFECT HYPOTHESIS Eugene Cha, John Sfakianos, Sasinya Scott, Paari Murugan, Gopa Iyer, Ronak Shah, Aditya Bagrodia, Neil Desai, Dean Bajorin, Jonathan Rosenberg, Michael Berger, Hikmat Al-Ahmadie, Bernard Bochner, Jonathan Coleman, and David Solit Eugene ChaEugene Cha More articles by this author , John SfakianosJohn Sfakianos More articles by this author , Sasinya ScottSasinya Scott More articles by this author , Paari MuruganPaari Murugan More articles by this author , Gopa IyerGopa Iyer More articles by this author , Ronak ShahRonak Shah More articles by this author , Aditya BagrodiaAditya Bagrodia More articles by this author , Neil DesaiNeil Desai More articles by this author , Dean BajorinDean Bajorin More articles by this author , Jonathan RosenbergJonathan Rosenberg More articles by this author , Michael BergerMichael Berger More articles by this author , Hikmat Al-AhmadieHikmat Al-Ahmadie More articles by this author , Bernard BochnerBernard Bochner More articles by this author , Jonathan ColemanJonathan Coleman More articles by this author , and David SolitDavid Solit More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.740AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Urothelial carcinoma is characterized by multifocal and metachronous tumors. To explain this phenomenon, two hypotheses have been proposed: the ‘field defect’ hypothesis - urothelial cells are primed to undergo transformation by exposure to carcinogens, and the clonal, or ‘single progenitor cell,’ hypothesis - tumors arise from intraluminal seeding of transformed cells. We sought to examine the clonal relationships between primary upper tract urothelial carcinoma (UTUC) tumors and metachronous bladder tumors (intravesical recurrences) in patients treated with radical nephroureterectomy (RNU) and subsequent transurethral resection. METHODS Tumor and germline DNA was extracted from surgical specimens and analyzed using a next-generation, targeted sequencing assay designed to identify point mutations, indels, and copy number alterations in 341 cancer-associated genes. The somatic mutation profiles of primary UTUC tumors and subsequent bladder tumors were compared in individual patients. RESULTS We analyzed 16 primary UTUC tumors and 41 intravesical recurrences in 16 patients treated with RNU. The median number of intravesical recurrences per patient was 2 (range 1-7) and the interval from RNU to intravesical recurrence ranged from 3.5 months to 129 months. With an average sequencing coverage of 516x, we found strong evidence delineating the clonal relationship between primary UTUC tumors and subsequent bladder tumors. The majority of somatic mutations present in the primary UTUC tumors (median=7, range 4-39) were detected in all subsequent bladder tumors (128/146, 88%). In an illustrative case, one patient followed with periodic cystoscopy/cytology who had been NED for 5.5 years then developed 7 bladder tumors over the next 44 months, each with the identical mutation profile (8 mutations) as the primary tumor. CONCLUSIONS We demonstrate that bladder tumors following RNU represent true intravesical recurrences, with almost all tumors sharing the same somatic mutation profile as the primary UTUC tumor. This has important implications for surgical techniques to minimize the risk of intraluminal seeding, the delivery of intravesical therapy following RNU, and the development of strategies employing systemic chemotherapy or targeted agents. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e433 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Eugene Cha More articles by this author John Sfakianos More articles by this author Sasinya Scott More articles by this author Paari Murugan More articles by this author Gopa Iyer More articles by this author Ronak Shah More articles by this author Aditya Bagrodia More articles by this author Neil Desai More articles by this author Dean Bajorin More articles by this author Jonathan Rosenberg More articles by this author Michael Berger More articles by this author Hikmat Al-Ahmadie More articles by this author Bernard Bochner More articles by this author Jonathan Coleman More articles by this author David Solit More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...