MP08-08 GENOMIC LANDSCAPE AND MOLECULAR CHARACTERIZATION OF RENAL CELL CARCINOMA IN DIALYSIS PATIENTS

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology I (MP08)1 Apr 2020MP08-08 GENOMIC LANDSCAPE AND MOLECULAR CHARACTERIZATION OF RENAL CELL CARCINOMA IN DIALYSIS PATIENTS Ryohei Takahashi*, Nobuyuki Tanaka, Fuyuki Miya, Takashi Kamatani, Toshikazu Takeda, Kazuhiro Matsumoto, Shinya Morita, Takeo Kosaka, Ryuichi Mizuno, Shuji Mikami, Kazuhiro Kakimi, Tatsuhiko Tsunoda, and Mototsugu Oya Ryohei Takahashi*Ryohei Takahashi* More articles by this author , Nobuyuki TanakaNobuyuki Tanaka More articles by this author , Fuyuki MiyaFuyuki Miya More articles by this author , Takashi KamataniTakashi Kamatani More articles by this author , Toshikazu TakedaToshikazu Takeda More articles by this author , Kazuhiro MatsumotoKazuhiro Matsumoto More articles by this author , Shinya MoritaShinya Morita More articles by this author , Takeo KosakaTakeo Kosaka More articles by this author , Ryuichi MizunoRyuichi Mizuno More articles by this author , Shuji MikamiShuji Mikami More articles by this author , Kazuhiro KakimiKazuhiro Kakimi More articles by this author , Tatsuhiko TsunodaTatsuhiko Tsunoda More articles by this author , and Mototsugu OyaMototsugu Oya More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000828.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The number of chronic renal failure has been rapidly growing. Further, not only in advanced nations, the number of dialysis patients continues to increase explosively even though in a developing nation. It’s evident that long-term dialysis induces the onset of renal cell carcinomas (RCCs). Marked differences in the genetic and epigenetic backgrounds of cancer cells have been revealed by advances in genome sequencing in various cancer types, yet little is known about those landscapes of RCC in dialysis patients. Herein, we show an integrated genomic and molecular study using to 40 dialysis patient RCC specimens, clarifying the tumor biology and identifying potential therapeutic targets for RCCs under dialysis. METHODS: In total, we conducted whole-exome sequencing (n=20) with paired normal DNA, RNA sequencing (n=14), comprehensive DNA methylation microarray (n=25), or immunohistochemistry (n=35). Notably, assessing recent immune-checkpoint targets e.g., CD3, CD8, CD20, CTLA4, FOXP3, PD-1, and PD-L1 expression, we histologically characterized the tumor immune microenvironment in dialysis patient RCCs. RESULTS: Whole-exome sequencing detected 55.5 somatic mutations per tumor, and ninety-four mutated genes were overlapped in multiple cases. The VHL somatic mutations were found in 58% of clear cell RCCs (ccRCCs) occurred in dialysis patients. Rather, no apparent difference was found comparing to the COSMIC database. Further, PBRM1 and SETD2 somatic mutations were found in 17% and 8% of dialysis patient ccRCC, respectively. Conversely, no VHL somatic mutation was not found in RCC related to acquired cystic disease of the kidney (n=6). CONCLUSIONS: Inactivation of VHL gene is an archetypical tumor-initiating event in ccRCC. Also, our subset of ccRCC occurred in dialysis patients was favored by VHL somatic mutations in tumorgenesis, suggesting that oncogenic mechanisms of ccRCC may be similar under dialysis. However, RCC in dialysis patients must be a global concern, thus further study should be warranted. Source of Funding: none © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e108-e109 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ryohei Takahashi* More articles by this author Nobuyuki Tanaka More articles by this author Fuyuki Miya More articles by this author Takashi Kamatani More articles by this author Toshikazu Takeda More articles by this author Kazuhiro Matsumoto More articles by this author Shinya Morita More articles by this author Takeo Kosaka More articles by this author Ryuichi Mizuno More articles by this author Shuji Mikami More articles by this author Kazuhiro Kakimi More articles by this author Tatsuhiko Tsunoda More articles by this author Mototsugu Oya More articles by this author Expand All Advertisement PDF downloadLoading ...