MP18-14 CHARACTERISING DNA METHYLATION PATTERNS IN TISSUE AND CIRCULATING TUMOUR DNA TO ENABLE DIFFERENTIATION OF SMALL RENAL MASSES

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology II (MP18)1 Apr 2020MP18-14 CHARACTERISING DNA METHYLATION PATTERNS IN TISSUE AND CIRCULATING TUMOUR DNA TO ENABLE DIFFERENTIATION OF SMALL RENAL MASSES Sabrina Rossi*, Sara Pita, Anne Babbage, Gahee Park, Radoslaw Lach, Christopher Smith, Kevin Brennan, Tom Mitchell, Anne Warren, Olivier Gevaert, Charlie Massie, Grant Stewart, and DIAMOND Biobank Study Group Sabrina Rossi*Sabrina Rossi* More articles by this author , Sara PitaSara Pita More articles by this author , Anne BabbageAnne Babbage More articles by this author , Gahee ParkGahee Park More articles by this author , Radoslaw LachRadoslaw Lach More articles by this author , Christopher SmithChristopher Smith More articles by this author , Kevin BrennanKevin Brennan More articles by this author , Tom MitchellTom Mitchell More articles by this author , Anne WarrenAnne Warren More articles by this author , Olivier GevaertOlivier Gevaert More articles by this author , Charlie MassieCharlie Massie More articles by this author , Grant StewartGrant Stewart More articles by this author , and DIAMOND Biobank Study GroupDIAMOND Biobank Study Group More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000843.014AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Small renal masses (SRM) represent a diagnostic challenge. Indeed, ∼20% of SRM removed at surgery are found to be benign post-operatively. Renal biopsy may be non-diagnostic due to small tumour size, challenging anatomy or tumour heterogeneity. Circulating tumour DNA (ctDNA) analysis of DNA methylation in plasma or urine may overcome sampling bias associated with genetic intratumoral heterogeneity and offer a non-invasive method to derive a diagnosis. To test whether epigenetic markers differentiate pathological subtypes of renal masses we aim to (a) analyse multi-region samples from patients with renal tumours to map the landscape of DNA methylation heterogeneity and (b) evaluate methylation markers in triplicates of tissue, plasma and urine. METHODS: We recruited a cohort of patients across the RCC disease spectrum, from small renal masses to metastatic disease, including different pathological subtypes. Ethical approval was obtained (DIAMOND biobank; REC ID 03/018). Multi-region kidney tumour samples were collected from the nephrectomy specimen, including adjacent normal tissue, as well as urine and plasma samples from the same patients. Methylation analysis was performed in tissue using the Illumina EPIC Methyl Capture library preparation kit, with post capture bisulfite conversion. RESULTS: Tumour and normal samples were collected from 75 individuals with clear cell (N=35), chromophobe (N=10), papillary (N=20) RCC and oncocytoma (N=10). Additionally, we sequenced 142 multi-region samples from a subset of 26 patients and performed epigenetic phylogenetic analyses. We identified sets of differentially methylated cytosines at base-pair resolution in tumour tissue that (a) classify pathological subtypes of RCC and oncocytomas and (b) represent early ‘stem’ markers for ctDNA analysis. We present a summary of epigenetic clonal evolution and identify markers for high-sensitivity targeted analysis of DNA methylation in liquid samples. CONCLUSIONS: We evaluate DNA methylation in a large cohort of patients with pathological subtypes of renal tumours. This may represent a promising target for non-invasive liquid biopsy to differentiate benign from malignant small renal masses. Source of Funding: SHR is funded by a Cancer Research UK PhD Fellowship. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e240-e241 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sabrina Rossi* More articles by this author Sara Pita More articles by this author Anne Babbage More articles by this author Gahee Park More articles by this author Radoslaw Lach More articles by this author Christopher Smith More articles by this author Kevin Brennan More articles by this author Tom Mitchell More articles by this author Anne Warren More articles by this author Olivier Gevaert More articles by this author Charlie Massie More articles by this author Grant Stewart More articles by this author DIAMOND Biobank Study Group More articles by this author Expand All Advertisement PDF downloadLoading ...