MP01-12 DETECTION OF UROTHELIAL CARCINOMA BASED ON COPY NUMBER PROFILES OF URINARY CFDNA USING SHALLOW WHOLE-GENOME SEQUENCING

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology I (MP01)1 Apr 2020MP01-12 DETECTION OF UROTHELIAL CARCINOMA BASED ON COPY NUMBER PROFILES OF URINARY CFDNA USING SHALLOW WHOLE-GENOME SEQUENCING Yanqing Gong*, Guangzhe Ge, Ding Peng, Bao Guan, Yuanyuan Zhou, Weimin Ci, Xuesong Li, and Liqun Zhou Yanqing Gong*Yanqing Gong* More articles by this author , Guangzhe GeGuangzhe Ge More articles by this author , Ding PengDing Peng More articles by this author , Bao GuanBao Guan More articles by this author , Yuanyuan ZhouYuanyuan Zhou More articles by this author , Weimin CiWeimin Ci More articles by this author , Xuesong LiXuesong Li More articles by this author , and Liqun ZhouLiqun Zhou More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000815.012AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Current non-invasive assays for urothelial cancer (UC) lack sensitivity and specificity. Given the utility of plasma cell-free DNA (cfDNA) biomarkers, the development of urinary cfDNA biomarkers may improve the diagnostic sensitivity. METHODS: We assessed copy number aberrations (CNAs) by shallow genome-wide sequencing of urinary cfDNA in 95 cancer-free individuals and 65 UC, 58 kidney cancer and 45 prostate cancer patients. We used a support vector machine (SVM) to develop a diagnostic classifier based on CNA profiles to detect UC (UCdetector). The model was further validated in an independent cohort (52 cases). Genome sequencing data of tumor specimens from 90 upper tract urothelial cancers (UTUC) and CNA data for 410 urothelial carcinomas of bladder (UCB) from TCGA were used to validate the classifier. Genome sequencing data for urine sediments of 32 UC patients were compared with cfDNA. To monitor the treatment efficacy, we collected cfDNA from 7 post-treatment patients. RESULTS: We showed that urinary cfDNA could be a more sensitive alternative to urinary sediment. The UCdetector can detect UC at a median sensitivity of 86.5% and specificity of 94.7%. The UCdetector performed well in an independent validation dataset. Notably, the CNA features selected by UCdetector were specific markers for both UTUC and UCB. Moreover, the CNA changes in cfDNA were consistent with the treatment effects. Meanwhile, the same strategy could localize genitourinary cancers to tissue-of-origin in 70.1% of patients. CONCLUSIONS: Our findings underscore the potential utility of urinary cfDNA CNA profiles as a basis for non-invasive UC detection and surveillance. Source of Funding: This work was supported by CAS Strategic Priority Research Program (XDA16010102 to W.C.), the National Key R&D Program of China (2018YFC2000100 to W.C.), CAS (QYZDB-SSW-SMC039 to W.C.), the National Natural Science Foundation of China (81672541 to W.C.), and K.C.Wong Education Foundation to W.C. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e6-e6 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yanqing Gong* More articles by this author Guangzhe Ge More articles by this author Ding Peng More articles by this author Bao Guan More articles by this author Yuanyuan Zhou More articles by this author Weimin Ci More articles by this author Xuesong Li More articles by this author Liqun Zhou More articles by this author Expand All Advertisement PDF downloadLoading ...