PD46-07 URINARY COMPREHENSIVE GENOMIC PROFILING AIDS IN DETECTION AND RISK PROGNOSIS OF UPPER TRACT UROTHELIAL CARCINOMA: A CASE-CONTROLLED COHORT STUDY

Abstract

You have accessJournal of UrologyCME1 Apr 2023PD46-07 URINARY COMPREHENSIVE GENOMIC PROFILING AIDS IN DETECTION AND RISK PROGNOSIS OF UPPER TRACT UROTHELIAL CARCINOMA: A CASE-CONTROLLED COHORT STUDY Paul Yonover, Robert Kaplinsky, Keyan Salari, Adam Feldman, Debasish Sundi, Kevin G. Phillips, Daniel Fisher, Ava Cherry, Brian C. Mazzarella, Vincent T. Bicocca, Joe Gray, Theresa M. Koppie, Trevor G. Levin, and Justin Cohen Paul YonoverPaul Yonover More articles by this author , Robert KaplinskyRobert Kaplinsky More articles by this author , Keyan SalariKeyan Salari More articles by this author , Adam FeldmanAdam Feldman More articles by this author , Debasish SundiDebasish Sundi More articles by this author , Kevin G. PhillipsKevin G. Phillips More articles by this author , Daniel FisherDaniel Fisher More articles by this author , Ava CherryAva Cherry More articles by this author , Brian C. MazzarellaBrian C. Mazzarella More articles by this author , Vincent T. BicoccaVincent T. Bicocca More articles by this author , Joe GrayJoe Gray More articles by this author , Theresa M. KoppieTheresa M. Koppie More articles by this author , Trevor G. LevinTrevor G. Levin More articles by this author , and Justin CohenJustin Cohen More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003359.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: A urine test capable of detecting upper tract urothelial carcinoma (UTUC) that provides diagnostic and prognostic information might aid diagnosis and improve risk stratification, which are major clinical challenges in UTUC. Urinary comprehensive genomic profiling (uCGP) via next-generation sequencing with the CLIA-validated UroAmp assay (Convergent Genomics) was developed to identify mutations, diagnose disease, assess molecular grade and stage, and predict recurrence risk. Here we verify that a urine-based uCGP approach can identify lesions in UTUC patients and we compare these genomic profiles to subjects with bladder cancer. METHODS: uCGP was performed on 69 specimens from individuals with de novo pathology-confirmed UC of the bladder (UCB) and 12 urine specimens from individuals with de novo pathology-confirmed UTUC. Urine DNA was sequenced, comprehensively profiled across 60 genes, and disease classification was predicted by a machine learned algorithm. Differential mutational signals of UTUC and UCB were compared through odds ratio (OR) analysis with statistical significance ascribed by Fisher’s exact test. RESULTS: Among UTUC patients, grade distribution was 83% HG, 17% LG; stage distribution was 25% Ta, 25% T1, 8% T2, 8% T3, 8% T4, 25% unknown; among UCB patients grade distribution was 70% HG, 30% LG; stage distribution was 45% Ta, 22% T1, 20% T2, 7% T4, 4% Tis, 2% unknown. uCGP correctly classified 100% of UTUC subjects and 97% (67/69) of UCB subjects as disease positive. UTUC lesions had a high prevalence of TP53 mutations (70%) and frequently demonstrated genomic instability with large scale aneuploidy (40%), loss of heterozygosity (30%), ERCC2 amplification (30%), and CDKN2A loss (10%). Additional recurrent mutations included KMT2C (40%), KMT2D (40%), FGFR3 (30%), and TERT (30%). OR analysis revealed significant enrichment of promoter mutations in TERT (OR=10.6) among high grade (HG) UCB lesions compared to HG UTUC. Further, mutations in ARID1A, PLEKHS1, were solely observed in HG UCB lesions. CONCLUSIONS: uCGP is a quantitative diagnostic with the ability to profile genomic lesions in UTUC and UCB. While further study is needed, distinct mutational patterns in UTUC could potentially serve to identify urologic origins of urine-based disease signals. Source of Funding: Research support by Convergent Genomics © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1172 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Paul Yonover More articles by this author Robert Kaplinsky More articles by this author Keyan Salari More articles by this author Adam Feldman More articles by this author Debasish Sundi More articles by this author Kevin G. Phillips More articles by this author Daniel Fisher More articles by this author Ava Cherry More articles by this author Brian C. Mazzarella More articles by this author Vincent T. Bicocca More articles by this author Joe Gray More articles by this author Theresa M. Koppie More articles by this author Trevor G. Levin More articles by this author Justin Cohen More articles by this author Expand All Advertisement PDF downloadLoading ...