LBA-14 COMPREHENSIVE CHARACTERISATION OF CIRCULATING TUMOUR DNA IN PLASMA AND URINE OF PATIENTS WITH RENAL TUMOURS - RESULTS OF THE DIAMOND AND MONREC STUDIES
At a Glance
Section titled “At a Glance”| Metadata | Details |
|---|---|
| Publication Date | 2019-04-01 |
| Journal | The Journal of Urology |
| Authors | Christopher R. Smith, Ellen Heitzer, Tina Moser, Florent Moulière, Dineika Chandrananda |
Abstract
Section titled “Abstract”You have accessJournal of UrologySunday Next Frontier (LBA)1 Apr 2019LBA-14 COMPREHENSIVE CHARACTERISATION OF CIRCULATING TUMOUR DNA IN PLASMA AND URINE OF PATIENTS WITH RENAL TUMOURS: RESULTS OF THE DIAMOND AND MONREC STUDIES Christopher Smith, Ellen Heitzer, Tina Moser, Florent Mouliere, Dineika Chandrananda, Tom Mitchell, Anne Warren, Johanna Burge, James Armitage, Tony Riddick, Tev Aho, Matthew Eldridge, Charlie Massie, Nitzan Rosenfeld, and Grant* Stewart Christopher SmithChristopher Smith More articles by this author , Ellen HeitzerEllen Heitzer More articles by this author , Tina MoserTina Moser More articles by this author , Florent MouliereFlorent Mouliere More articles by this author , Dineika ChandranandaDineika Chandrananda More articles by this author , Tom MitchellTom Mitchell More articles by this author , Anne WarrenAnne Warren More articles by this author , Johanna BurgeJohanna Burge More articles by this author , James ArmitageJames Armitage More articles by this author , Tony RiddickTony Riddick More articles by this author , Tev AhoTev Aho More articles by this author , Matthew EldridgeMatthew Eldridge More articles by this author , Charlie MassieCharlie Massie More articles by this author , Nitzan RosenfeldNitzan Rosenfeld More articles by this author , and Grant* StewartGrant* Stewart More articles by this author View All Author Informationhttps://doi.org/10.1097/01.JU.0000557506.46205.f9AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVES: Cell-free tumour derived DNA (ctDNA) has been demonstrated to allow non-invasive detection and tracking of various cancers. However, the utility of ctDNA in RCC has not been well established, here we describe the DIAMOND and MonReC studies which were designed in order to undertake a detailed analysis of baseline and longitudinal cfDNA in RCC. METHODS: We characterised the levels and composition of ctDNA in longitudinally collected plasma and urine of patients with renal tumours: DIAMOND included 47 patients with a range of renal tumours, and MonReC 43 patients with metastatic RCCs. Untargeted approaches, including shallow Whole Genome Sequencing, sWGS, and modified Fast Aneuploidy Screen Test-Sequencing System, mFAST-Seq, were initially applied. Targeted methods including a novel analysis algorithm termed INtegration of VAriant Reads from TArgeted PAnel Sequencing, INVAR-TAPAS, and Qiagen’s QIASeq custom capture panel were used for sensitive ctDNA detection. RESULTS: Untargeted sequencing methods revealed that ctDNA levels are lower and present in a lower proportion of RCC patient than other cancers of similar stage, detecting ctDNA in the plasma and/or urine of 16/47 (34%) patients from DIAMOND and in plasma of 14/43 (33%) in MonReC. The use of increasingly sensitive targeted approaches saw detection in the plasma and/or urine of DIAMOND patients increase to 52% (24/47), and 34.5% (15/43) in the plasma of patients from MonReC. Tumours were significantly larger amongst patients with detectable ctDNA as compared to those without. A fragmentation feature based random forest model was capable of triaging patients with detectable ctDNA levels from their sWGS ctDNA profile. Further interrogation of those patients with detectable ctDNA revealed, for the first time, that urine ctDNA is capable of overcoming genetic heterogeneity and offers information that is complementary to that provided by plasma. Furthermore, longitudinal sampling of >200 plasma and urine samples revealed that in a subset of patients ctDNA can be used to track disease course, as well as indicate clonal evolution of the growing lesion. CONCLUSIONS: This data, generated using state-of-the-art techniques, confirm that ctDNA can be detected in blood and urine of RCC patients, albeit that in the majority of cases highly sensitive techniques are required. Improved isolation and detection approaches, combined with methods for appropriate triaging of patients will ensure that the potential of ctDNA for the clinical management of RCC patients will be realised. Source of Funding: CRUK Cambridge Institute, ERC, Addenbrooke’s Charitable Trust, Renal Cancer Research Fund, Austrian Science Fund, Christian Doppler Research Fund Cambridge, United Kingdom; Graz, Austria; Cambridge, United Kingdom© 2019 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 201Issue Supplement 4April 2019Page: e998-e998 Advertisement Copyright & Permissions© 2019 by American Urological Association Education and Research, Inc.MetricsAuthor Information Christopher Smith More articles by this author Ellen Heitzer More articles by this author Tina Moser More articles by this author Florent Mouliere More articles by this author Dineika Chandrananda More articles by this author Tom Mitchell More articles by this author Anne Warren More articles by this author Johanna Burge More articles by this author James Armitage More articles by this author Tony Riddick More articles by this author Tev Aho More articles by this author Matthew Eldridge More articles by this author Charlie Massie More articles by this author Nitzan Rosenfeld More articles by this author Grant* Stewart More articles by this author Expand All Advertisement PDF downloadLoading …