title: Unreserved application of epigenetic methods to define differences of DNA methylation between urinary cellular and cell-free DNA.
abstract: Urinary DNA is increasingly gaining importance in diagnosis of urological malignancies. Especially cell-free DNA originating from apoptotic and necrotic cells of the early tumor could become a key target for early stage tumor diagnosis. Aberrant DNA methylation forms tumor cell characteristic epigenetic profiles which are covalently established before any tumor related aberration at transcriptional or protein level has occurred. In addition, these epigenetic signatures are alterably adapted to and accompanying the individual stages of multistep, progressive tumorigenesis. Hence, they seem very promising for diagnosis as well as for monitoring the patient's follow-up care and even for decisions regarding personalized therapeutic options. The essential prerequisite at this approach will be a reliable methodological handling of the biological material of interest. In this study we present detailed analyses of LINE-1 DNA methylation profiles and demonstrate the sensitive detection of LINE-1 DNA methylation differences as well as between cancer patients and healthy individuals, between urinary cellular and cell-free DNA. In addition, we show methylome differences between both DNA fractions from a healthy individual and bladder cancer patients. In conclusion, we demonstrate here the unrestricted amenability of urinary cell-free DNA for both, a detailed characterization of a distinct DNA methylation alteration and its sensitive detection and a comprehensive global, array-based screening for DNA methylation differences.
authors.affiliation: Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Foued
authors.initials: F
authors.lastname: Ghanjati
authors.affiliation: Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Agnes
authors.initials: A
authors.lastname: Beermann
authors.affiliation: Department of Urology, University Hospital Zürich, Zürich, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hermanns
authors.affiliation: Department of Urology, University Hospital Zürich, Zürich, Switzerland.
authors.forename: Cedric
authors.initials: C
authors.lastname: Poyet
authors.affiliation: Group of Computational Biology and Systems Biomedicine, Biodonostia Health Research Institute, San Sebastián, Spain IKERBASQUE, Basque Foundation for Science, Bilbao, Spain.
authors.forename: Marcos J
authors.initials: MJ
authors.lastname: Araúzo-Bravo
authors.affiliation: Hegau-Bodensee-Hospital, Singen, Germany.
authors.forename: Hans-Helge
authors.initials: HH
authors.lastname: Seifert
authors.affiliation: Department of Urology, University Hospital Zürich, Zürich, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Schmidtpeter
authors.affiliation: Department of Urology, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Goering
authors.affiliation: Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Sorg
authors.affiliation: Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Wernet
authors.affiliation: Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Simeon
authors.initials: S
authors.lastname: Santourlidis
mesh_terms: D016022:Case-Control Studies; D002474:Cell-Free System / Q000502:physiology*; D004247:DNA / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics*; D006801:Humans; D001743:Urinary Bladder / Q000502:physiology*; D001749:Urinary Bladder Neoplasms / Q000235:genetics
chemical_list: D004247:DNA
keywords: Cell-free DNA; DNA methylation; bladder cancer; diagnosis; urine