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BMC Genomics. 2015 May 22;16:403. doi: 10.1186/s12864-015-1450-3.

The UBC-40 Urothelial Bladder Cancer cell line index: a genomic resource for functional studies.

Author information

1
Epithelial Carcinogenesis Group, F BBVA Cancer Cell Biology Programme, CNIO (Spanish National Cancer Research Centre), Madrid, Spain. jearl@ext.cnio.es.
2
Servicio de Oncología Médica, Hospital Ramón y Cajal, Madrid, Spain. jearl@ext.cnio.es.
3
Structural Computational Biology Group, Structural Biology and Biocomputing Programme, CNIO (Spanish National Cancer Research Centre), Madrid, Spain. drico@cnio.es.
4
Epithelial Carcinogenesis Group, F BBVA Cancer Cell Biology Programme, CNIO (Spanish National Cancer Research Centre), Madrid, Spain. ecarrillo@cnio.es.
5
Quantitative Genomic Medicine Laboratory, qGenomics, Barcelona, Spain. benjamin.rodriguez@qgenomics.com.
6
Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain. benjamin.rodriguez@qgenomics.com.
7
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain. benjamin.rodriguez@qgenomics.com.
8
Epithelial Carcinogenesis Group, F BBVA Cancer Cell Biology Programme, CNIO (Spanish National Cancer Research Centre), Madrid, Spain. mmendez@cnio.es.
9
Institut de Recerca Biomèdica de Barcelona, Parc Científic de Barcelona, Barcelona, Spain. herbert.auer@irbbarcelona.org.
10
Bioinformatics Unit, Structural Biology and Biocomputing Programme, CNIO (Spanish National Cancer Research Centre), Madrid, Spain. ggomez@cnio.es.
11
Department of Urology, MD Anderson Cancer Center, Houston, TX, USA. hbgrossman@mdanderson.org.
12
Bioinformatics Unit, Structural Biology and Biocomputing Programme, CNIO (Spanish National Cancer Research Centre), Madrid, Spain. dgpisano@cnio.es.
13
Department of Urology, Heinrich-Heine-University, Düsseldorf, Germany. wolfgang.schulz@uni-duesseldorf.de.
14
Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain. luis.perez@upf.edu.
15
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain. luis.perez@upf.edu.
16
Servicio de Oncología Médica, Hospital Ramón y Cajal, Madrid, Spain. acarrato@telefonica.net.
17
University of Colorado Comprehensive Cancer Center, 80045, Aurora, CO, USA. dan.theodorescu@ucdenver.edu.
18
Translational Genomics Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, USA. chanocks@mail.nih.gov.
19
Structural Computational Biology Group, Structural Biology and Biocomputing Programme, CNIO (Spanish National Cancer Research Centre), Madrid, Spain. avalencia@cnio.es.
20
Epithelial Carcinogenesis Group, F BBVA Cancer Cell Biology Programme, CNIO (Spanish National Cancer Research Centre), Madrid, Spain. preal@cnio.es.
21
Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain. preal@cnio.es.
22
Cancer Cell Biology Programme, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, 28029, Madrid, Spain. preal@cnio.es.

Abstract

BACKGROUND:

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.

RESULTS:

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.

CONCLUSIONS:

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.

PMID:
25997541
PMCID:
PMC4470036
DOI:
10.1186/s12864-015-1450-3
[Indexed for MEDLINE]
Free PMC Article

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