title: Genomic complexity of urothelial bladder cancer revealed in urinary cfDNA.
abstract: Urothelial bladder cancers (UBCs) have heterogeneous clinical characteristics that are mirrored in their diverse genomic profiles. Genomic profiling of UBCs has the potential to benefit routine clinical practice by providing prognostic utility above and beyond conventional clinicopathological factors, and allowing for prediction and surveillance of treatment responses. Urinary DNAs representative of the tumour genome provide a promising resource as a liquid biopsy for non-invasive genomic profiling of UBCs. We compared the genomic profiles of urinary cellular DNA and cell-free DNA (cfDNA) from the urine with matched diagnostic formalin-fixed paraffin-embedded tumour DNAs for 23 well-characterised UBC patients. Our data show urinary DNAs to be highly representative of patient tumours, allowing for detection of recurrent clinically actionable genomic aberrations. Furthermore, a greater aberrant load (indicative of tumour genome) was observed in cfDNA over cellular DNA (P<0.001), resulting in a higher analytical sensitivity for detection of clinically actionable genomic aberrations (P<0.04) when using cfDNA. Thus, cfDNA extracted from the urine of UBC patients has a higher tumour genome burden and allows greater detection of key genomic biomarkers (90%) than cellular DNA from urine (61%) and provides a promising resource for robust whole-genome tumour profiling of UBC with potential to influence clinical decisions without invasive patient interventions.
authors.affiliation: West Midland Regional Genetics Laboratory, Birmingham Women's NHS Foundation Trust, Birmingham, UK.
authors.forename: Fiona S
authors.initials: FS
authors.lastname: Togneri
authors.affiliation: Institute of Cancer & Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Ward
authors.affiliation: Affymetrix UK Ltd, High Wycombe, UK.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Foster
authors.affiliation: Institute of Cancer & Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Devall
authors.affiliation: West Midland Regional Genetics Laboratory, Birmingham Women's NHS Foundation Trust, Birmingham, UK.
authors.forename: Paula
authors.initials: P
authors.lastname: Wojtowicz
authors.affiliation: West Midland Regional Genetics Laboratory, Birmingham Women's NHS Foundation Trust, Birmingham, UK.
authors.forename: Sofia
authors.initials: S
authors.lastname: Alyas
authors.affiliation: West Midland Regional Genetics Laboratory, Birmingham Women's NHS Foundation Trust, Birmingham, UK.
authors.forename: Fabiana Ramos
authors.initials: FR
authors.lastname: Vasques
authors.affiliation: Affymetrix UK Ltd, High Wycombe, UK.
authors.forename: Assa
authors.initials: A
authors.lastname: Oumie
authors.affiliation: Cancer Research Unit, University of Warwick, Coventry, UK.
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: James
authors.affiliation: School of Health and Population Sciences, University of Birmingham, Birmingham, UK.
authors.forename: K K
authors.initials: KK
authors.lastname: Cheng
authors.affiliation: Department of Complex Genetics, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, The Netherlands.
authors.forename: Maurice P
authors.initials: MP
authors.lastname: Zeegers
authors.affiliation: Institute of Cancer & Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Nayneeta
authors.initials: N
authors.lastname: Deshmukh
authors.affiliation: Department of Histopathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
authors.forename: Brendan
authors.initials: B
authors.lastname: O'Sullivan
authors.affiliation: Department of Histopathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
authors.forename: Philippe
authors.initials: P
authors.lastname: Taniere
authors.affiliation: Affymetrix UK Ltd, High Wycombe, UK.
authors.forename: Karen G
authors.initials: KG
authors.lastname: Spink
authors.affiliation: West Midland Regional Genetics Laboratory, Birmingham Women's NHS Foundation Trust, Birmingham, UK.
authors.forename: Dominic J
authors.initials: DJ
authors.lastname: McMullan
authors.affiliation: West Midland Regional Genetics Laboratory, Birmingham Women's NHS Foundation Trust, Birmingham, UK.
authors.forename: Mike
authors.initials: M
authors.lastname: Griffiths
authors.affiliation: Institute of Cancer & Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Bryan
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000652:urine*; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology / Q000652:urine; D002869:Chromosome Aberrations; D004273:DNA, Neoplasm / Q000235:genetics / Q000652:urine*; D015894:Genome, Human; D006801:Humans; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology / Q000652:urine; D019459:Urothelium / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm