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Genomic characterization of three urinary bladder cancer cell lines: understanding genomic types of urinary bladder cancer

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Tumor Biology

Abstract

Several genomic regions are frequently altered and associated with the type, stage and progression of urinary bladder cancer (UBC). We present the characterization of 5637, T24 and HT1376 UBC cell lines by karyotyping, fluorescence in situ hybridization (FISH), array comparative genomic hybridization (aCGH) and multiplex ligation-dependent probe amplification (MLPA) analysis. Some cytogenetic anomalies present in UBC were found in the three cell lines, such as chromosome 20 aneuploidy and the loss of 9p21. Some gene loci losses (e.g. CDKN2A) and gains (e.g. HRAS, BCL2L1 and PTPN1) were coincident across all cell lines. Although some significant heterogeneity and complexity were detected between them, their genomic profiles exhibited a similar pattern to UBC. We suggest that 5637 and HT1376 represent the E2F3/RB1 pathway due to amplification of 6p22.3, concomitant with loss of one copy of RB1 and mutation of the remaining copy. The HT1376 presented a 10q deletion involving PTEN region and no alteration of PIK3CA region which, in combination with the inactivation of TP53, bears more invasive and metastatic properties than 5637. The T24 belongs to the alternative pathway of FGFR3/CCND1 by presenting mutated HRAS and over-represented CCND1. These cell lines cover the more frequent subtypes of UBC and are reliable models that can be used, as a group, in preclinical studies.

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Acknowledgments

The authors express their deepest appreciation to Célia Carvalho of the Instituto de Medicina Molecular, Lisboa, Portugal, for review of the manuscript.

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Authors and Affiliations

  1. Cytogenetic Laboratory, Department of Human Genetics, Hospital Center of Trás-os-Montes and Alto Douro, Vila Real, Portugal

    Rosário Pinto-Leite, Jaqueline Ferreira & Marco Filipe

  2. Cytogenetics and Genomics Laboratory, Faculty of Medicine, University of Coimbra, Coimbra, Portugal

    Isabel Carreira, Joana Melo, Susana Isabel Ferreira & Ilda Ribeiro

  3. Center of Investigation on Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, Coimbra, Portugal

    Isabel Carreira, Joana Melo & Ilda Ribeiro

  4. Experimental Pathology and Therapeutics Group, Research Center, Portuguese Oncology Institute, Porto, Portugal

    Carina Bernardo & Lúcio Santos

  5. Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro, Vila Real, Portugal

    Regina Arantes-Rodrigues & Paula Oliveira

  6. Department of Surgical Oncology, Portuguese Institute of Oncology, Porto, Portugal

    Lúcio Santos

  7. Health Faculty, Fernando Pessoa University, Porto, Portugal

    Lúcio Santos

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  1. Rosário Pinto-Leite
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  2. Isabel Carreira
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Correspondence to Paula Oliveira.

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Pinto-Leite, R., Carreira, I., Melo, J. et al. Genomic characterization of three urinary bladder cancer cell lines: understanding genomic types of urinary bladder cancer. Tumor Biol. 35, 4599–4617 (2014). https://doi.org/10.1007/s13277-013-1604-3

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