PD17-05 GENOMIC FEATURES OF RENAL CELL CARCINOMA DEVELOPED DURING END-STAGE RENAL DISEASE AND DIALYSIS

Abstract

You have accessJournal of UrologyCME1 Apr 2023PD17-05 GENOMIC FEATURES OF RENAL CELL CARCINOMA DEVELOPED DURING END-STAGE RENAL DISEASE AND DIALYSIS Shigekatsu Maekawa, Todd Johnson, Masashi Fujita, Ryo Takata, Daiki Ikarashi, Tomohiko Matsuura, Renpei Kato, Mitsugu Kanehira, Jun Sugimura, Takaya Abe, Hikewaki Nakagawa, and Wataru Obara Shigekatsu MaekawaShigekatsu Maekawa More articles by this author , Todd JohnsonTodd Johnson More articles by this author , Masashi FujitaMasashi Fujita More articles by this author , Ryo TakataRyo Takata More articles by this author , Daiki IkarashiDaiki Ikarashi More articles by this author , Tomohiko MatsuuraTomohiko Matsuura More articles by this author , Renpei KatoRenpei Kato More articles by this author , Mitsugu KanehiraMitsugu Kanehira More articles by this author , Jun SugimuraJun Sugimura More articles by this author , Takaya AbeTakaya Abe More articles by this author , Hikewaki NakagawaHikewaki Nakagawa More articles by this author , and Wataru ObaraWataru Obara More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003272.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Patients with end-stage renal disease (ESRD) or receiving dialysis have a much higher risk for renal cell carcinoma (RCC), but carcinogenic mechanisms and genomic features remain little explored and undefined. This study’s goal was to identify the genomic features of ESRD RCC and characterize them for associations with tumor histology and dialysis exposure. In this study, we obtained 33 RCCs, with various histological subtypes, that developed in ESRD patients receiving dialysis and performed whole-genome sequencing and transcriptome analyses. METHODS: Frozen kidney samples were obtained from 48 patients who were undergoing dialysis treatment and developed RCC at Iwate Medical University Hospital. Among them, we selected 38 subjects for study from whom matched tumor and adjacent non-tumor tissue samples could be obtained and from which DNA (n=38) or RNA (n=26) could be isolated. We performed whole genome sequencing of genomic DNA using MGIEasy FS DNA Library Prep Set and short read sequencer DNBSEQ-G400. mRNA Sample were sequenced using HiSeq. Driver events, copy-number alteration (CNA) analysis, and mutational signature profiling was performed using an analysis pipeline that integrated data from germline and somatic SNVs, Indels, and structural variants as well as CNAs, while transcriptome data was analyzed for differentially expressed genes and through gene set enrichment analysis. RESULTS: ESRD related clear cell RCCs' driver genes and mutations mirrored those in sporadic ccRCCs. Longer dialysis periods significantly correlated with a rare mutational signature SBS23, whose etiology is unknown, and increased mitochondrial copy number. All ACD (acquired cystic disease)-RCCs, which developed specifically in ESRD patients, showed chromosome 16q amplification. Gene expression analysis suggests similarity between certain ACD-RCCs and papillary RCCs and in TCGA papillary RCCs with chromosome 16 gain identified enrichment for genes related to DNA repair, as well as pathways related to reactive oxygen species, oxidative phosphorylation, and targets of Myc. CONCLUSIONS: This analysis suggests that ESRD or dialysis could induce types of cellular stress that impact some specific types of genomic damage leading to oncogenesis. Source of Funding: none © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e497 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shigekatsu Maekawa More articles by this author Todd Johnson More articles by this author Masashi Fujita More articles by this author Ryo Takata More articles by this author Daiki Ikarashi More articles by this author Tomohiko Matsuura More articles by this author Renpei Kato More articles by this author Mitsugu Kanehira More articles by this author Jun Sugimura More articles by this author Takaya Abe More articles by this author Hikewaki Nakagawa More articles by this author Wataru Obara More articles by this author Expand All Advertisement PDF downloadLoading ...