MP54-16 URINARY EXOSOMAL AND CELL-FREE DNA DETECTS SOMATIC MUTATION AND COPY NUMBER ALTERATION IN UROTHELIAL CARCINOMA OF BLADDER

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology I1 Apr 2018MP54-16 URINARY EXOSOMAL AND CELL-FREE DNA DETECTS SOMATIC MUTATION AND COPY NUMBER ALTERATION IN UROTHELIAL CARCINOMA OF BLADDER Kwang Hyun Kim, Bong Suk Sim, and Dong Hyeon Lee Kwang Hyun KimKwang Hyun Kim More articles by this author , Bong Suk SimBong Suk Sim More articles by this author , and Dong Hyeon LeeDong Hyeon Lee More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1707AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Urothelial bladder canrcinoma (UBC) is characterized by a large number of genetic alteration. Urinary DNA is promising resources for liquid biopsy in urological malignancies. In this study, we performed genomic profiling of UBC and matched urinary cell free DNA (cfDNA) and exosomal DNA (exoDNA). METHODS We included 9 patients who underwent surgery for UBC. Fresh frozen tumor sample and normal blood sample was used for genomic profiling of UBC. We also performed genomic profiling of matched urinary DNA to investigate whether genomic alteration in tumor samples are echoed in urinary DNA. Urinary exoDNA was extracted from urinary exosome which was isolated by ExoQuick and urinary cfDNA was extracted by commercial kit using magnetic bead. We performed 9 gene target sequencing for somatic mutation analysis and low depth whole genome sequencing (ldWGS) for copy number analysis. RESULTS We found 17 somatic mutations in 6 patients, and 17 included 6 nonsynonymous SNVs, 3 stopgain SNVs, 2 frameshift deletion and 6 synonymous SNVs. Of 17 somatic mutations, 12 were identified in cfDNA and exoDNA with the mean allele frequency of 54.5% and 65.6%, respectively. Mean depth of cfDNA and exoDNA was 1721X and 1627X, respectively (Figure 1). In copy number analysis, mean 20.4% of whole genome region was covered by >1X. Copy number plots of cfDNA and exoDNA showed similar pattern with those of tumor samples. When we compare the log2 ratio of 100k bin size in whole genome regions, Pearson correlation coefficients of tumor vs cfDNA (0.481) and tumor vs exoDNA (0.455) were higher than that of tumor vs normal (0.086) (Figure 2). CONCLUSIONS Both urinary cfDNA and exoDNA were representative of the entire human genome and allowed genomic profiling of UBC. Specifically, copy number analysis using ldWGS has potential to be used as tools developing biomarker with low cost and whole genome coverage. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e718 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Kwang Hyun Kim More articles by this author Bong Suk Sim More articles by this author Dong Hyeon Lee More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...