MP49-01 NEXT GENERATION SEQUENCING OF CELL FREE DNA REVEALS GENOMIC ABERRATIONS IN METASTATIC UROTHELIAL CARCINOMA
2016-03-28

You have accessJournal of UrologyBladder Cancer: Invasive III1 Apr 2016MP49-01 NEXT GENERATION SEQUENCING OF CELL FREE DNA REVEALS GENOMIC ABERRATIONS IN METASTATIC UROTHELIAL CARCINOMA Tilman Todenhöfer, Stanislav Volik, Bernie Eigl, Scott North, Sonal Brahmbhatt, Anne Haegert, Johannes Mischinger, Arnulf Stenzl, Stephane LeBihan, Alexander Wyatt, Colin Collins, and Peter Black Tilman TodenhöferTilman Todenhöfer More articles by this author , Stanislav VolikStanislav Volik More articles by this author , Bernie EiglBernie Eigl More articles by this author , Scott NorthScott North More articles by this author , Sonal BrahmbhattSonal Brahmbhatt More articles by this author , Anne HaegertAnne Haegert More articles by this author , Johannes MischingerJohannes Mischinger More articles by this author , Arnulf StenzlArnulf Stenzl More articles by this author , Stephane LeBihanStephane LeBihan More articles by this author , Alexander WyattAlexander Wyatt More articles by this author , Colin CollinsColin Collins More articles by this author , and Peter BlackPeter Black More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.414AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To date, only limited data is available on genomic alterations present in metastatic lesions of patients with metastatic urothelial carcinoma (mUC). The constant release of circulating cell free DNA (cfDNA) from tumor cells into the peripheral blood stream may provide a valuable source for detection of cancer associated somatic copy number variations and mutations. The value of next-generation sequencing (NGS) of cfDNA to identify unknown genomic mutations in patients with bladder cancer has not been addressed. The aim of the present pilot study was to evaluate the feasibility of analysis of somatic mutations and copy number variations in plasma cfDNA of patients with mUC. METHODS Peripheral blood (20ml) was collected from 8 patients with mUC before chemotherapy. Plasma cfDNA was isolated using the QIAAmp Circulating Nucleic Acid Kit. DNA was extracted from peripheral blood mononuclear cells (PBMCs) using the DNEasy Kit (Qiagen) for assessment of germ-line DNA alterations. Library construction was performed using the Ampliseq Comprehensive Cancer Panel (ThermoFisher). NGS was done on an ION Proton platform (ThermoFisher). Copy number variations and mutations were compared to publically available datasets from UC tissue. RESULTS The median amount of cfDNA extracted was 202.2 ng (range 42.3-530.4). We detected strong mutation candidates in 6/8 patients (Table 1) and copy number changes consistent with previously reported alterations in UC. Common copy number variations included gain of 1p (5/8 patients), 7p (5/8 patients), and 17q (3/8 patients including one with high-level focal amplification of ERBB2) and loss of 6q (6/8 patients). CONCLUSIONS Non-invasive characterization of genomic changes in peripheral blood of patients with mUC using NGS of plasma cfDNA is feasible and detects copy number changes and mutations in a high proportion of patients. Analysis of cfDNA might therefore provide an improved understanding of genomic changes in mUC that could enable the personalized use of targeted therapies. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e664 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Tilman Todenhöfer More articles by this author Stanislav Volik More articles by this author Bernie Eigl More articles by this author Scott North More articles by this author Sonal Brahmbhatt More articles by this author Anne Haegert More articles by this author Johannes Mischinger More articles by this author Arnulf Stenzl More articles by this author Stephane LeBihan More articles by this author Alexander Wyatt More articles by this author Colin Collins More articles by this author Peter Black More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...