Pd48-08 Comparative Analysis of Methylation Biomarkers in Tumor and Urinary Tumor Dna in High-Risk Non-Muscle Invasive Bladder Cancer Patients

You have accessJournal of UrologyBladder Cancer: Non-invasive III (PD48)1 May 2024PD48-08 COMPARATIVE ANALYSIS OF METHYLATION BIOMARKERS IN TUMOR AND URINARY TUMOR DNA IN HIGH-RISK NON-MUSCLE INVASIVE BLADDER CANCER PATIENTS Hiroko Miyagi, Joshua Linscott, Billie Gould, Pan Du, Shidong Jia, and Roger Li Hiroko MiyagiHiroko Miyagi , Joshua LinscottJoshua Linscott , Billie GouldBillie Gould , Pan DuPan Du , Shidong JiaShidong Jia , and Roger LiRoger Li View All Author Informationhttps://doi.org/10.1097/01.JU.0001008712.53259.7d.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Alterations in DNA methylation are considered to be one of the earliest events in developing bladder cancer. Biomarkers that profile methylation patterns in urinary cell-free DNA represent a largely unexplored avenue for detecting urinary tumors. Here, we sought to evaluate the concordance of methylation patterns between tumor tissue DNA, plasma, and cell-free urinary tumor DNA (utDNA) in high-risk non-muscle invasive bladder cancer (NMIBC), demonstrating the potential utility of urinary epigenetic alterations as early indicators of disease. METHODS: Patients with high-risk NMIBC (n=49) were prospectively enrolled prior to repeat TURBT (rTURBT). PredicineEPIC™ genome-wide methylation assay was performed on matched index TURBT tissue (iTURBT, n=41), repeat TURBT tissue (rTURBT, n=28), pre-repeat TURBT urine (preUR, n=15), pre-repeat urine cell pellet (n=15), and pre-repeat plasma (n=15). The number of hypo- and hyper-methylated genomic regions was calculated probabilistically in comparison with data from a panel of 19 urine samples from healthy donors. Abnormal regions were annotated for any overlap with HG19 gene promoter regions. RESULTS: Concordance of matched samples was highest between preUR and rTURBT tissue (r=0.98). Interestingly, a slight negative correlation between iTURBT and rTURBT tissue was observed (r = -0.14). Low methylation signal concordance was observed between matched urine and plasma (r=0.11). For 4 patients with a full set of matched samples (iTURBT, rTURBT, preUR, plasma) there were 213 gene promoters abnormally methylated across 3 or more of the samples. Consistently abnormal gene promotor methylation was seen in APC, SOX2, and several HOXD-family genes across samples. CONCLUSIONS: We demonstrate the potential utility of urinary cell free DNA methylation patterns as a biomarker of disease in NMIBC patients prior to rTURBT. Urinary methylation patterns were highly concordant with patterns observed in patient rTURBT tissues. Drivers of alterations in methylation patterns from index to repeat TURBT tumor tissue remains to be explored further. Future applications require incorporation of urinary DNA methylation alterations with existing tools to improve use in diagnosis and surveillance. Download PPT Source of Funding: Predicine, Inc © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e991 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Hiroko Miyagi More articles by this author Joshua Linscott More articles by this author Billie Gould More articles by this author Pan Du More articles by this author Shidong Jia More articles by this author Roger Li More articles by this author Expand All Advertisement PDF downloadLoading ...