title: The UBC-40 Urothelial Bladder Cancer cell line index: a genomic resource for functional studies.
abstract: Urothelial bladder cancer is a highly heterogeneous disease. Cancer cell lines are useful tools for its study. This is a comprehensive genomic characterization of 40 urothelial bladder carcinoma (UBC) cell lines including information on origin, mutation status of genes implicated in bladder cancer (FGFR3, PIK3CA, TP53, and RAS), copy number alterations assessed using high density SNP arrays, uniparental disomy (UPD) events, and gene expression.
  
  
  
  Based on gene mutation patterns and genomic changes we identify lines representative of the FGFR3-driven tumor pathway and of the TP53/RB tumor suppressor-driven pathway. High-density array copy number analysis identified significant focal gains (1q32, 5p13.1-12, 7q11, and 7q33) and losses (i.e. 6p22.1) in regions altered in tumors but not previously described as affected in bladder cell lines. We also identify new evidence for frequent regions of UPD, often coinciding with regions reported to be lost in tumors. Previously undescribed chromosome X losses found in UBC lines also point to potential tumor suppressor genes. Cell lines representative of the FGFR3-driven pathway showed a lower number of UPD events.
  
  
  
  Overall, there is a predominance of more aggressive tumor subtypes among the cell lines. We provide a cell line classification that establishes their relatedness to the major molecularly-defined bladder tumor subtypes. The compiled information should serve as a useful reference to the bladder cancer research community and should help to select cell lines appropriate for the functional analysis of bladder cancer genes, for example those being identified through massive parallel sequencing.
authors.affiliation: Epithelial Carcinogenesis Group, F BBVA Cancer Cell Biology Programme, CNIO (Spanish National Cancer Research Centre), Madrid, Spain. jearl@ext.cnio.es.|Servicio de Oncología Médica, Hospital Ramón y Cajal, Madrid, Spain. jearl@ext.cnio.es.
authors.forename: Julie
authors.initials: J
authors.lastname: Earl
authors.affiliation: Structural Computational Biology Group, Structural Biology and Biocomputing Programme, CNIO (Spanish National Cancer Research Centre), Madrid, Spain. drico@cnio.es.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rico
authors.affiliation: Epithelial Carcinogenesis Group, F BBVA Cancer Cell Biology Programme, CNIO (Spanish National Cancer Research Centre), Madrid, Spain. ecarrillo@cnio.es.
authors.forename: Enrique
authors.initials: E
authors.lastname: Carrillo-de-Santa-Pau
authors.affiliation: Quantitative Genomic Medicine Laboratory, qGenomics, Barcelona, Spain. benjamin.rodriguez@qgenomics.com.|Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain. benjamin.rodriguez@qgenomics.com.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain. benjamin.rodriguez@qgenomics.com.
authors.forename: Benjamín
authors.initials: B
authors.lastname: Rodríguez-Santiago
authors.affiliation: Epithelial Carcinogenesis Group, F BBVA Cancer Cell Biology Programme, CNIO (Spanish National Cancer Research Centre), Madrid, Spain. mmendez@cnio.es.
authors.forename: Marinela
authors.initials: M
authors.lastname: Méndez-Pertuz
authors.affiliation: Institut de Recerca Biomèdica de Barcelona, Parc Científic de Barcelona, Barcelona, Spain. herbert.auer@irbbarcelona.org.
authors.forename: Herbert
authors.initials: H
authors.lastname: Auer
authors.affiliation: Bioinformatics Unit, Structural Biology and Biocomputing Programme, CNIO (Spanish National Cancer Research Centre), Madrid, Spain. ggomez@cnio.es.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Gómez
authors.affiliation: Department of Urology, MD Anderson Cancer Center, Houston, TX, USA. hbgrossman@mdanderson.org.
authors.forename: Herbert Barton
authors.initials: HB
authors.lastname: Grossman
authors.affiliation: Bioinformatics Unit, Structural Biology and Biocomputing Programme, CNIO (Spanish National Cancer Research Centre), Madrid, Spain. dgpisano@cnio.es.
authors.forename: David G
authors.initials: DG
authors.lastname: Pisano
authors.affiliation: Department of Urology, Heinrich-Heine-University, Düsseldorf, Germany. wolfgang.schulz@uni-duesseldorf.de.
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Schulz
authors.affiliation: Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain. luis.perez@upf.edu.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain. luis.perez@upf.edu.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Pérez-Jurado
authors.affiliation: Servicio de Oncología Médica, Hospital Ramón y Cajal, Madrid, Spain. acarrato@telefonica.net.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Carrato
authors.affiliation: University of Colorado Comprehensive Cancer Center, 80045, Aurora, CO, USA. dan.theodorescu@ucdenver.edu.
authors.forename: Dan
authors.initials: D
authors.lastname: Theodorescu
authors.affiliation: Translational Genomics Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, USA. chanocks@mail.nih.gov.
authors.forename: Stephen
authors.initials: S
authors.lastname: Chanock
authors.affiliation: Structural Computational Biology Group, Structural Biology and Biocomputing Programme, CNIO (Spanish National Cancer Research Centre), Madrid, Spain. avalencia@cnio.es.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Valencia
authors.affiliation: Epithelial Carcinogenesis Group, F BBVA Cancer Cell Biology Programme, CNIO (Spanish National Cancer Research Centre), Madrid, Spain. preal@cnio.es.|Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain. preal@cnio.es.|Cancer Cell Biology Programme, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, 28029, Madrid, Spain. preal@cnio.es.
authors.forename: Francisco X
authors.initials: FX
authors.lastname: Real
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D045744:Cell Line, Tumor; D041321:Chromosomes, Human, X; D058534:Class I Phosphatidylinositol 3-Kinases; D016000:Cluster Analysis; D056915:DNA Copy Number Variations; D030541:Databases, Genetic; D005260:Female; D015894:Genome, Human; D042822:Genomic Instability; D006801:Humans; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology; D018631:ras Proteins / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3; D018631:ras Proteins