PD49-03 GENETIC AND EPIGENETIC PROFILING INDICATES THE PROXIMAL TUBULE ORIGIN OF RENAL CANCERS IN END-STAGE RENAL DISEASE

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology II (PD49)1 Sep 2021PD49-03 GENETIC AND EPIGENETIC PROFILING INDICATES THE PROXIMAL TUBULE ORIGIN OF RENAL CANCERS IN END-STAGE RENAL DISEASE Hiroki Ishihara, Satoshi Yamashita, Yu-Yu Liu, Naoko Hattori, Omar El-Omar, Takashi Ikeda, Hironori Fukuda, Kazuhiko Yoshida, Toshio Takagi, Sekiko Taneda, Tsunenori Kondo, Yoji Nagashima, Kazunari Tanabe, and Toshikazu Ushijima Hiroki IshiharaHiroki Ishihara More articles by this author , Satoshi YamashitaSatoshi Yamashita More articles by this author , Yu-Yu LiuYu-Yu Liu More articles by this author , Naoko HattoriNaoko Hattori More articles by this author , Omar El-OmarOmar El-Omar More articles by this author , Takashi IkedaTakashi Ikeda More articles by this author , Hironori FukudaHironori Fukuda More articles by this author , Kazuhiko YoshidaKazuhiko Yoshida More articles by this author , Toshio TakagiToshio Takagi More articles by this author , Sekiko TanedaSekiko Taneda More articles by this author , Tsunenori KondoTsunenori Kondo More articles by this author , Yoji NagashimaYoji Nagashima More articles by this author , Kazunari TanabeKazunari Tanabe More articles by this author , and Toshikazu UshijimaToshikazu Ushijima More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002071.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: End-stage renal disease (ESRD) patients on dialysis therapy have a higher incidence of renal cell carcinomas (RCCs), which consist of two major histopathological types: clear-cell RCCs (ESRD-ccRCCs) and acquired cystic disease (ACD)-associated RCCs. However, their genetic and epigenetic alterations are still poorly understood. METHODS: We investigated somatic mutations, copy number alterations (CNAs), and DNA methylation profiles in 9 ESRD-ccRCCs and 7 ACD-associated RCCs to identify their molecular alterations and cellular origins. RESULTS: Targeted sequencing of 409 cancer-related genes, including VHL, PBRM1, SETD2, BAP1, KDM5C, MET, KMT2C (MLL3), and TP53, showed ESRD-ccRCCs harbored frequent VHL mutations while ACD-associated RCCs did not. CNA analysis showed that ESRD-ccRCCs had a frequent loss of chromosome 3p while ACD-associated RCCs had a gain of chromosome 16. Beadarray methylation analysis showed that ESRD-ccRCCs had methylation profiles similar to those of sporadic ccRCCs while ACD-associated RCCs had profiles similar to those of papillary RCCs (Figure 1). Expression analysis of genes whose expression levels are characteristic to individual segments of a nephron showed that ESRD-ccRCCs and ACD-associated RCCs had high expressions of proximal tubule cell marker genes while chromophobe RCCs had high expressions of distal tubule cell/collecting duct cell marker genes (Figures 2 and 3). CONCLUSIONS: ESRD-ccRCCs and ACD-associated RCCs had mutation and methylation profiles similar to those of sporadic ccRCCs and papillary RCCs, respectively, and these two histopathological types of RCCs were indicated to have originated from proximal tubule cells of the nephron. Source of Funding: This research was supported by AMED under Grant Number JP19cm0106451 to Toshikazu Ushijima, JSPS KAKENHI under Grant Number JP18H02704 to Toshikazu Ushijima, and JSPS KAKENHI under Grant Number 17K11162 to Yoji Nagashima © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e844-e845 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hiroki Ishihara More articles by this author Satoshi Yamashita More articles by this author Yu-Yu Liu More articles by this author Naoko Hattori More articles by this author Omar El-Omar More articles by this author Takashi Ikeda More articles by this author Hironori Fukuda More articles by this author Kazuhiko Yoshida More articles by this author Toshio Takagi More articles by this author Sekiko Taneda More articles by this author Tsunenori Kondo More articles by this author Yoji Nagashima More articles by this author Kazunari Tanabe More articles by this author Toshikazu Ushijima More articles by this author Expand All Advertisement Loading ...