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• W3188202287 abstract "You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology III (MP66)1 Sep 2021MP66-05 TERT PROMOTER MUTATION IN GENOMIC EVOLUTION OF UROTHELIAL BLADDER CANCER: PHYLOGENETIC TREE MODEL BY ALGORITHMIC INFERENCE FROM CROSS-SECTIONAL DATA Yujiro Hayashi, Kazutoshi Fujita, Eri Banno, Marie Eich, Gaku Yamamichi, Satoru Yumiba, Eisuke Tomiyama, Yoko Koh, Makoto Matsushita, Kosuke Nakano, Taigo Kato, Koji Hatano, Atsunari Kawashima, Motohide Uemura, George Netto, and Norio Nonomura Yujiro HayashiYujiro Hayashi More articles by this author , Kazutoshi FujitaKazutoshi Fujita More articles by this author , Eri BannoEri Banno More articles by this author , Marie EichMarie Eich More articles by this author , Gaku YamamichiGaku Yamamichi More articles by this author , Satoru YumibaSatoru Yumiba More articles by this author , Eisuke TomiyamaEisuke Tomiyama More articles by this author , Yoko KohYoko Koh More articles by this author , Makoto MatsushitaMakoto Matsushita More articles by this author , Kosuke NakanoKosuke Nakano More articles by this author , Taigo KatoTaigo Kato More articles by this author , Koji HatanoKoji Hatano More articles by this author , Atsunari KawashimaAtsunari Kawashima More articles by this author , Motohide UemuraMotohide Uemura More articles by this author , George NettoGeorge Netto More articles by this author , and Norio NonomuraNorio Nonomura More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002106.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Tumorigenesis is a multistep process that involves accumulation of somatic mutations or epigenetic changes in the cancer-associated genes. We reported that TERT promoter mutation in non-malignant urothelium of patients with urothelial bladder cancer (UBC) was significantly associated with bladder tumor recurrence after transurethral surgery. Thus, TERT promoter mutations might play a significant role in UBC tumorigenesis. However, collection of longitudinal samples from a single malignant patient over a long period of tumorigenesis poses as the major challenge in studying tumor evolution. We aim to investigate the association between genomic evolution and TERT promoter mutation in UBC using algorithmic inference form cross-sectional data. METHODS: We performed algorithmic inference on 193 UBC specimens composed from three independent cohorts. One hundred five non-muscle invasive bladder cancer (NMIBC) specimens sequenced by MSK-IMPACT panel (NMI-MSKCC cohort), 54 NMIBC specimens sequenced by UROSEEK panel (NMI-UROSEEK cohort), and 34 muscle invasive bladder cancer (MIBC) specimens sequenced by UROSEEK panel (MI-UROSEEK cohort) were accessed to mutation-based progression analysis. We used Cancer Progression Inference (CAPRI) based on bootstrap and hypothesis testing for efficient algorithm inference of cancer progression from cross-sectional data. RESULTS: The frequency of gene mutations was 73%, 48% and 38% in the TERT promoter; 21% 24%, and 50% in TP53; 45%, 28%, and 9% in FGFR3 in NMI-MSKCC, NMI-UROSEEK, and MI-UROSEEK cohorts, respectively. In NMI-MSKCC cohort, the TERT promoter, TP53, and PIK3CA mutations were evident during the early stages of cancer progression. The analysis of NMI-MSKCC also showed that chromatin-modifying gene mutations, such as KDM6A, KMT2D, or ARID1A occurred late in the NMIBC tumorigenesis. TERT promoter and TP53 mutations also occurred as an early event during tumorigenesis in NMI-UROSEEK and MI-UROSEEK cohorts, followed by other gene mutations. CONCLUSIONS: By using algorithmic inference, we showed TERT promoter may play an important role in UBC tumorigenesis. Source of Funding: This study was supported by JSPS KAKENHI Grant Number JP 20K18139 © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1130-e1131 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yujiro Hayashi More articles by this author Kazutoshi Fujita More articles by this author Eri Banno More articles by this author Marie Eich More articles by this author Gaku Yamamichi More articles by this author Satoru Yumiba More articles by this author Eisuke Tomiyama More articles by this author Yoko Koh More articles by this author Makoto Matsushita More articles by this author Kosuke Nakano More articles by this author Taigo Kato More articles by this author Koji Hatano More articles by this author Atsunari Kawashima More articles by this author Motohide Uemura More articles by this author George Netto More articles by this author Norio Nonomura More articles by this author Expand All Advertisement PDF downloadLoading ..." @default.
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• W3188202287 title "MP66-05 TERT PROMOTER MUTATION IN GENOMIC EVOLUTION OF UROTHELIAL BLADDER CANCER: PHYLOGENETIC TREE MODEL BY ALGORITHMIC INFERENCE FROM CROSS-SECTIONAL DATA" @default.
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