Abstract
Bladder cancer (BC) remains an aggressive disease with a poor prognosis, especially for patients with metastatic disease who have a limited median overall survival of 14 months. Urothelial carcinomas harbor frequent molecular dysregulations including recurrent mutations and copy number alteration, some of which could be potential therapeutic targets. However, no molecularly targeted agents have been approved to date for the treatment of advanced BC. Gaining new insights into the molecular landscape of BC will be critical to tailor future targeted agents for the treatment of advanced disease. The Cancer Genome Atlas (TCGA) project is cataloguing the genetic and epigenetic alterations responsible for cancer through the application of high-throughput genome analysis techniques. After the landmark paper profiling 131 patients was published in 2014, additional patients have been added with an updated TCGA analysis now including 412 patients. This chapter will review the previously described genomic alterations reported in the first manuscript and the new major highlights found in the expanded analyses recently published. The aim will be to review how this comprehensive integrated genomic analysis can inform the design of precision medicine targeted therapy for the treatment of advanced disease.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Sobin LH, Gospodariwicz M, Wittekind C (eds) (2009) TNM classification of malignant tumors. UICC International Union Against Cancer, 7th edn. Wiley-Blackwell, pp 262–265
Witjes JA, Compérat E, Cowan NC et al (2014) EAU guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2013 guidelines. Eur Urol 65(4):778–792
Loehrer PJ, Einhorn LH, Elson PJ et al (1992) A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study. J Clin Oncol 10(7):1066–1073
von der Maase H, Sengelov L, Roberts JT et al (2005) Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol 23(21):4602–4608
Goebell PJ, Knowles MA (2010) Bladder cancer or bladder cancers? Genetically distinct malignant conditions of the urothelium. Urol Oncol 28(4):409–428
Forbes SA, Bindal N, Bamford S et al (2011) COSMIC: mining complete cancer genomes in the catalogue of somatic mutations in cancer. Nucleic Acids Res 39(Database issue):D945–950
Lindgren D, Sjödahl G, Lauss M et al (2012) Integrated genomic and gene expression profiling identifies two major genomic circuits in urothelial carcinoma. PLoS ONE 7(6):e38863
Hurst CD, Platt FM, Taylor CF, Knowles MA (2012) Novel tumor subgroups of urothelial carcinoma of the bladder defined by integrated genomic analysis. Clin Cancer Res 18(21):5865–5877
van Rhijn BW, Lurkin I, Radvanyi F, Kirkels WJ, van der Kwast TH, Zwarthoff EC (2001) The fibroblast growth factor receptor 3 (FGFR3) mutation is a strong indicator of superficial bladder cancer with low recurrence rate. Cancer Res 61(4):1265–1268
Knowles MA, Hurst CD (2015) Molecular biology of bladder cancer: new insights into pathogenesis and clinical diversity. Nat Rev Cancer 15(1):25–41
Bellmunt J, de Wit R, Vaughn DJ et al (2017) Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med
https://cancergenome.nih.gov/. Last accessed June 2017
https://tcga-data.nci.nih.gov/docs/publications/tcga/. Last accessed June 2017
Network CGAR (2014) Comprehensive molecular characterization of urothelial bladder carcinoma. Nature 507(7492):315–322
Robertson G, Kim J, Al-Ahmadie H et al (2017) Comprehensive molecular characterization of muscle-invasive urothelial carcinoma. Cell
Rosenberg JE, Hoffman-Censits J, Powles T et al (2016) Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet 387(10031):1909–1920
Balar AV, Galsky MD, Rosenberg JE et al (2016) Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet
Lawrence MS, Stojanov P, Polak P et al (2013) Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature 499(7457):214–218
Yang Y, Pang Z, Ding N et al (2016) The efficacy and potential predictive factors of PD-1/PD-L1 blockades in epithelial carcinoma patients: a systematic review and meta analysis. Oncotarget 7(45):74350–74361
Choi W, Czerniak B, Ochoa A et al (2014) Intrinsic basal and luminal subtypes of muscle-invasive bladder cancer. Nat Rev Urol 11(7):400–410
Choi W, Porten S, Kim S et al (2014) Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. Cancer Cell 25(2):152–165
Sjödahl G, Lauss M, Lövgren K et al (2012) A molecular taxonomy for urothelial carcinoma. Clin Cancer Res 18(12):3377–3386
Network CGA (2012) Comprehensive molecular portraits of human breast tumours. Nature 490(7418):61–70
Network CGAR (2012) Comprehensive genomic characterization of squamous cell lung cancers. Nature 489(7417):519–525
Filippakopoulos P, Qi J, Picaud S et al (2010) Selective inhibition of BET bromodomains. Nature 468(7327):1067–1073
Wu X, Liu D, Tao D et al (2016) BRD4 regulates EZH2 transcription through upregulation of C-MYC and represents a novel therapeutic target in bladder cancer. Mol Cancer Ther 15(5):1029–1042
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG, part of Springer Nature
About this chapter
Cite this chapter
Rodriguez-Vida, A., Lerner, S.P., Bellmunt, J. (2018). The Cancer Genome Atlas Project in Bladder Cancer. In: Daneshmand, S., Chan, K. (eds) Genitourinary Cancers . Cancer Treatment and Research, vol 175. Springer, Cham. https://doi.org/10.1007/978-3-319-93339-9_12
Download citation
DOI: https://doi.org/10.1007/978-3-319-93339-9_12
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-93338-2
Online ISBN: 978-3-319-93339-9
eBook Packages: MedicineMedicine (R0)