recurrence throughmodification by a common polymorphism. Proc
Natl Acad Sci U S A 2013;110:17426–31.
[48]
Vinagre J, Almeida A, Populo H, et al. Frequency of TERT promoter mutations in human cancers. Nat Commun 2013;4:2185.[49]
Cappellen D, De Oliveira C, Ricol D, et al. Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas. Nat Genet 1999;23:18–20.[50]
van Rhijn BW, Lurkin I, Radvanyi F, Kirkels WJ, van der Kwast TH, Zwarthoff EC. The fibroblast growth factor receptor 3 (FGFR3) mutation is a strong indicator of superficial bladder cancer with low recurrence rate. Cancer Res 2001;61:1265–8.[51]
Lamont FR, Tomlinson DC, Cooper PA, Shnyder SD, Chester JD, Knowles MA. Small molecule FGF receptor inhibitors block FGFR- dependent urothelial carcinoma growth in vitro and in vivo. Br J Cancer 2011;104:75–82.
[52]
di Martino E, L’Hote CG, Kennedy W, Tomlinson DC, Knowles MA. Mutant fibroblast growth factor receptor 3 induces intracellular signaling and cellular transformation in a cell type- and mutation- specific manner. Oncogene 2009;28:4306–16.[53]
Williams SV, Hurst CD, Knowles MA. Oncogenic FGFR3 gene fusions in bladder cancer. Hum Mol Gen 2013;22:795–803.[54]
Rampias T, Vgenopoulou P, Avgeris M, et al. A new tumor suppres- sor role for the Notch pathway in bladder cancer. Nat Med 2014;20:1199–205.[55]
Maraver A, Fernandez-Marcos PJ, Cash TP, et al. NOTCH pathway inactivation promotes bladder cancer progression. J Clin Invest 2015;125:824–30.[56]
Shin K, Lim A, Odegaard JI, et al. Cellular origin of bladder neoplasia and tissue dynamics of its progression to invasive carcinoma. Nat Cell Biol 2014;16:469–78.[57]
Shin K, Lim A, Zhao C, et al. Hedgehog signaling restrains bladder cancer progression by eliciting stromal production of urothelial differentiation factors. Cancer Cell 2014;26:521–33.[58]
Dyrskjot L, Thykjaer T, Kruhoffer M, et al. Identifying distinct classes of bladder carcinoma using microarrays. Nat Genet 2003;33:90–6.
[59]
Blaveri E, Simko JP, Korkola JE, et al. Bladder cancer outcome and subtype classification by gene expression. Clin Cancer Res 2005;11:4044–55.
[60]
Sanchez-Carbayo M, Socci ND, Lozano J, Saint F, Cordon-Cardo C. Defining molecular profiles of poor outcome in patients with invasive bladder cancer using oligonucleotide microarrays. J Clin Oncol 2006;24:778–89.[61]
Dyrskjot L, Kruhoffer M, Thykjaer T, et al. Gene expression in the urinary bladder: a common carcinoma in situ gene expression signature exists disregarding histopathological classification. Can- cer Res 2004;64:4040–8.[62]
Dyrskjot L, Zieger K, Kruhoffer M, et al. A molecular signature in superficial bladder carcinoma predicts clinical outcome. Clin Can- cer Res 2005;11:4029–36.[63]
Dyrskjot L, Zieger K, Real FX, et al. Gene expression signatures predict outcome in non-muscle-invasive bladder carcinoma: a multicenter validation study. Clin Cancer Res 2007;13:3545–51.[64]
Patschan O, Sjodahl G, Chebil G, et al. A molecular pathologic framework for risk stratification of stage T1 urothelial carcinoma. Eur Urol 2015;68:824–32, discussion 35–6.
[65]
Sjodahl G, Lauss M, Lovgren K, et al. A molecular taxonomy for urothelial carcinoma. Clin Cancer Res 2012;18:3377–86.
[66]
Sjodahl G, Lovgren K, Lauss M, et al. Toward a molecular pathologic classification of urothelial carcinoma. Am J Pathol 2013;183:681–91.[67]
Choi W, Porten S, Kim S, et al. Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. Cancer Cell 2014;25: 152–65.[68]
Damrauer JS, Hoadley KA, Chism DD, et al. Intrinsic subtypes of high-grade bladder cancer reflect the hallmarks of breast cancer biology. Proc Natl Acad Sci U S A 2014;111:3110–5.[69]
Aine M, Eriksson P, Liedberg F, Sjodahl G, Hoglund M. Biological determinants of bladder cancer gene expression subtypes. Sci Rep 2015;5:10957.[70]
Choi W, Czerniak B, Ochoa A, et al. Intrinsic basal and luminal subtypes of muscle-invasive bladder cancer. Nat Rev Urol 2014;11:400–10.[71]
McConkey DJ, Choi W, Dinney CP. New insights into subtypes of invasive bladder cancer: considerations of the clinician. Eur Urol 2014;66:609–10.
[72]
Rebouissou S, Bernard-Pierrot I, de Reynies A, et al. EGFR as a potential therapeutic target for a subset of muscle-invasive bladder cancers presenting a basal-like phenotype. Sci Transl Med 2014;6:244ra91.[73]
McConkey DJ, Choi W, Shen Y, et al. A prognostic gene expres- sion signature in the molecular classification of chemotherapy- naive urothelial cancer is predictive of clinical outcomes from neoadjuvant chemotherapy: a phase 2 trial of dose-dense meth- otrexate, vinblastine, doxorubicin, and cisplatin with bevacizu- mab in urothelial cancer. Eur Urol 2016;69:855–62.
[74]
McConkey DJ, Choi W, Ochoa A, Siefker-Radtke A, Czerniak B, Dinney CP. Therapeutic opportunities in the intrinsic subtypes of muscle-invasive bladder cancer. Hematol Oncol Clin North Am 2015;29:377–94, x–xi.[75]
Rosenberg JE, Hoffman-Censits J, Powles T, et al. 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 2016;387:1909–20.[76]
Kardos J, Chai S, Mose LE, et al. Claudin-low bladder tumors are immune infiltrated and actively immune suppressed. JCI Insight 2016;1:e85902.[77]
Mak MP, Tong P, Diao L, et al. A patient-derived, pan-cancer EMT signature identifies global molecular alterations and immune tar- get enrichment following epithelial-to-mesenchymal transition. Clin Cancer Res 2016;22:609–20.[78]
Lerner SP, McConkey DJ, Hoadley KA, et al. Bladder cancer molecu- lar taxonomy: summary from a consensus meeting. Bladder Cancer 2016;2:37–47.[79]
Ellis MJ, Perou CM. The genomic landscape of breast cancer as a therapeutic roadmap. Cancer Discov 2013;3:27–34.[80]
The Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature 2012;490:61–70.[81]
Bock M, Hinley J, Schmitt C, Wahlicht T, Kramer S, Southgate J. Identification of ELF3 as an early transcriptional regulator of human urothelium. Dev Biol 2014;386:321–30.
[82]
Varley CL, Stahlschmidt J, Lee WC, et al. Role of PPARgamma and EGFR signalling in the urothelial terminal differentiation pro- gramme. J Cell Sci 2004;117:2029–36.
[83]
Groenendijk FH, de Jong J, Fransen van de Putte EE, et al. ERBB2 mutations characterize a subgroup of muscle-invasive bladder cancers with excellent response to neoadjuvant chemotherapy. Eur Urol 2016;69:384–8.[84]
Van Batavia J, Yamany T, Molotkov A, et al. Bladder cancers arise from distinct urothelial sub-populations. Nat Cell Biol 2014;16:982–91, 1–5.
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