Skip to main content
SpringerLink
Log in

Urothelial Bladder Cancer: Genomic Alterations in Fibroblast Growth Factor Receptor

  • Original Research Article
  • Published:
Molecular Diagnosis & Therapy Aims and scope Submit manuscript

Abstract

Background and Objective

Genomic alterations in fibroblast growth factor receptor (FGFR) genes have been linked to a reduced response to immune checkpoint inhibitors. Some of the immune microenvironment of urothelial bladder cancer (UBC) could be distorted because of the inhibition of interferon signaling pathways. We present a landscape of FGFR genomic alterations in distorted UBC to evaluate the immunogenomic mechanisms of resistance and response.

Methods

There were 4035 UBCs that underwent hybrid, capture-based comprehensive genomic profiling. Tumor mutational burden was determined in up to 1.1 Mbp of sequenced DNA and microsatellite instability was determined in 114 loci. Programmed death ligand expression in tumor cells was assessed by immunohistochemistry (Dako 22C3).

Results

The FGFR tyrosine kinases were altered in 894 (22%) UBCs. The highest frequency of alterations was in FGFR genomic alterations with FGFR3 at 17.4% followed by FGFR1 at 3.7% and FGFR2 at 1.1%. No FGFR4 genomic alterations were identified. The age and sex distribution were similar in all groups. Urothelial bladder cancers that featured FGFR3 genomic alterations were associated with lower driver genomic alterations/tumors. 14.7% of the FGFR3 genomic alterations were FGFR3 fusions. Other findings included a significantly higher frequency of ERBB2 amplification in FGFR1/2-altered UBCs compared with FGFR3-altered UBCs. Urothelial bladder cancers with FGFR3 genomic alterations also had the highest frequency of the activating mTOR pathway. FGFR3-altered UBCs also featured significantly higher frequencies of biomarkers associated with a lack of response to immune checkpoint inhibitors including a lower tumor mutational burden, lower programmed death-ligand 1 expression, and higher frequencies of genomic alterations in MDM2. Also linked to IO drug resistance, CDKN2A/B loss and MTAP loss were observed at a higher frequency in FGFR3-driven UBC.

Conclusions

An increased frequency of genomic alterations is observed in UBC FGFR. These have been linked to immune checkpoint inhibitor resistance. Clinical trials are needed to evaluate UBC FGFR-based biomarkers prognostic of an immune checkpoint inhibitor response. Only then can we successfully incorporate novel therapeutic strategies into the evolving landscape of UBC treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Abd El-Salam MA, Smith CE, Pan CX. Insights on recent innovations in bladder cancer immunotherapy. Cancer Cytopathol. 2022;130(9):667–83.

    Article  CAS  PubMed  Google Scholar 

  2. Schneider AK, Chevalier MF, Derré L. The multifaceted immune regulation of bladder cancer. Nat Rev Urol. 2019;16(10):613–30.

    Article  CAS  PubMed  Google Scholar 

  3. Mendiratta P, Grivas P. Emerging biomarkers and targeted therapies in urothelial carcinoma. Ann Transl Med. 2018;6(12):250.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Patel VG, Oh WK, Galsky MD. Treatment of muscle-invasive and advanced bladder cancer in 2020. CA Cancer J Clin. 2020;70(5):404–23.

    Article  PubMed  Google Scholar 

  5. Ku JH, Seo HK, Kang SH. Where are we now and where are we heading in muscle invasive bladder cancer. Transl Androl Urol. 2020;9(6):2864.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Kim HS, Seo HK. Emerging treatments for bacillus Calmette–Guérin-unresponsive non-muscle-invasive bladder cancer. Invest Clin Urol. 2021;62(4):361.

    Article  Google Scholar 

  7. Bajorin DF, Witjes JA, Gschwend JE, Schenker M, Valderrama BP, Tomita Y, et al. Adjuvant nivolumab versus placebo in muscle-invasive urothelial carcinoma. N Engl J Med. 2021;384(22):2102–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Calò B, Marchioni M, Sanguedolce F, Falagario UG, Chirico M, Carrieri G, et al. Neoadjuvant chemotherapy before radical cystectomy: why we must adhere? Curr Drug Targets. 2021;22(1):14–21.

    Article  PubMed  Google Scholar 

  9. Necchi A, Anichini A, Raggi D, Briganti A, Massa S, Lucianò R, et al. Pembrolizumab as neoadjuvant therapy before radical cystectomy in patients with muscle-invasive urothelial bladder carcinoma (PURE-01): an open-label, single-arm, phase II study. J Clin Oncol. 2018;36(34):3353–60.

    Article  CAS  PubMed  Google Scholar 

  10. Powles T, Kockx M, Rodriguez-Vida A, Duran I, Crabb SJ, Van Der Heijden MS, et al. Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial. Nat Med. 2019;25(11):1706–14.

    Article  CAS  PubMed  Google Scholar 

  11. Necchi A, Raggi D, Gallina A, Madison R, Colecchia M, Lucianò R, et al. Updated results of PURE-01 with preliminary activity of neoadjuvant pembrolizumab in patients with muscle-invasive bladder carcinoma with variant histologies. Eur Urol. 2020;77(4):439–46.

    Article  CAS  PubMed  Google Scholar 

  12. Bandini M, Gibb EA, Gallina A, Raggi D, Marandino L, Bianchi M, et al. Does the administration of preoperative pembrolizumab lead to sustained remission post-cystectomy? First survival outcomes from the PURE-01 study. Ann Oncol. 2020;31(12):1755–63.

    Article  CAS  PubMed  Google Scholar 

  13. Gao J, Navai N, Alhalabi O, Siefker-Radtke A, Campbell MT, Tidwell RS, et al. Neoadjuvant PD-L1 plus CTLA-4 blockade in patients with cisplatin-ineligible operable high-risk urothelial carcinoma. Nat Med. 2020;26(12):1845–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. van Dijk N, Gil-Jimenez A, Silina K, Hendricksen K, Smit LA, de Feijter JM, et al. Preoperative ipilimumab plus nivolumab in locoregionally advanced urothelial cancer: the NABUCCO trial. Nat Med. 2020;26(12):1839–44.

    Article  PubMed  Google Scholar 

  15. Rose TL, Harrison MR, Deal AM, Ramalingam S, Whang YE, Brower B, et al. Phase II study of gemcitabine and split-dose cisplatin plus pembrolizumab as neoadjuvant therapy before radical cystectomy in patients with muscle-invasive bladder cancer. J Clin Oncol. 2021;39(28):3140–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Funt SA, Lattanzi M, Whiting K, Al-Ahmadie H, Quinlan C, Teo MY, et al. Neoadjuvant atezolizumab with gemcitabine and cisplatin in patients with muscle-invasive bladder cancer: a multicenter, single-arm, phase II trial. J Clin Oncol. 2022;40(12):1312–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Gupta S, Sonpavde G, Weight CJ, McGregor BA, Gupta S, Maughan BL, et al. Results from BLASST-1 (Bladder Cancer Signal Seeking Trial) of nivolumab, gemcitabine, and cisplatin in muscle invasive bladder cancer (MIBC) undergoing cystectomy. J Clin Oncol. 2020;38(6_Suppl):439.

    Article  Google Scholar 

  18. Kwon W-A, Seo HK. Optimizing frontline therapy in advanced urothelial cancer. Transl Androl Urol. 2020;9(3):983.

    Article  PubMed  PubMed Central  Google Scholar 

  19. D’Angelo A, Bagby S, Galli IC, Bortoletti C, Roviello G. Overview of the clinical use of erdafitinib as a treatment option for the metastatic urothelial carcinoma: where do we stand. Expert Rev Clin Pharmacol. 2020;13(10):1139–46.

    Article  PubMed  Google Scholar 

  20. Loriot Y, Necchi A, Park SH, Garcia-Donas J, Huddart R, Burgess E, et al. Erdafitinib in locally advanced or metastatic urothelial carcinoma. N Engl J Med. 2019;381(4):338–48.

    Article  CAS  PubMed  Google Scholar 

  21. Bou Zerdan M, Bratslavsky G, Jacob JM, Huang RS, Kravtsov O, Parimi V, et al. Landscape of fibroblast growth factor receptor (FGFR) genomic alterations (GA) in urothelial bladder cancer (UBC). 2022.

  22. Frampton GM, Fichtenholtz A, Otto GA, Wang K, Downing SR, He J, et al. Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing. Nat Biotechnol. 2013;31(11):1023–31. https://doi.org/10.1038/nbt.2696.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Chalmers ZR, Connelly CF, Fabrizio D, Gay L, Ali SM, Ennis R, et al. Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med. 2017;9(1):1–14.

    Article  Google Scholar 

  24. Trabucco SE, Gowen K, Maund SL, Sanford E, Fabrizio DA, Hall MJ, et al. A novel next-generation sequencing approach to detecting microsatellite instability and pan-tumor characterization of 1000 microsatellite instability-high cases in 67,000 patient samples. J Mol Diagn. 2019;21(6):1053–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Katoh M. FGFR inhibitors: effects on cancer cells, tumor microenvironment and whole-body homeostasis. Int J Mol Med. 2016;38(1):3–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Lemmon MA, Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell. 2010;141(7):1117–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Katoh M, Nakagama H. FGF receptors: cancer biology and therapeutics. Med Res Rev. 2014;34(2):280–300.

    Article  CAS  PubMed  Google Scholar 

  28. Brooks AN, Kilgour E, Smith PD. Molecular pathways: fibroblast growth factor signaling: a new therapeutic opportunity in cancerFGF/FGFR signaling in cancer. Clin Cancer Res. 2012;18(7):1855–62.

    Article  CAS  PubMed  Google Scholar 

  29. Knowles MA, Hurst CD. Molecular biology of bladder cancer: new insights into pathogenesis and clinical diversity. Nat Rev Cancer. 2015;15(1):2541.

    Article  Google Scholar 

  30. Liu S-B, Lu L-F, Lu X-B, Li S, Zhang Y-A. Zebrafish FGFR3 is a negative regulator of RLR pathway to decrease IFN expression. Fish Shellfish Immunol. 2019;92:224–9.

    Article  CAS  PubMed  Google Scholar 

  31. Xie K-Y, Wang Q, Cao D-J, Liu J, Xie X-F. Spinal astrocytic FGFR3 activation leads to mechanical hypersensitivity by increased TNF-α in spared nerve injury. Int J Clin Exp Pathol. 2019;12(8):2898.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Sweis RF, Spranger S, Bao R, Paner GP, Stadler WM, Steinberg G, et al. Molecular drivers of the non-T-cell-inflamed tumor microenvironment in urothelial bladder cancer drivers of non-T-cell-inflamed bladder cancer. Cancer Immunol Res. 2016;4(7):563–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Siemers NO, Holloway JL, Chang H, Chasalow SD, Ross-MacDonald PB, Voliva CF, et al. Genome-wide association analysis identifies genetic correlates of immune infiltrates in solid tumors. PLoS ONE. 2017;12(7): e0179726.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Chen S, Zhang N, Shao J, Wang T, Wang X. Multi-omics perspective on the tumor microenvironment based on PD-L1 and CD8 T-cell infiltration in urothelial cancer. J Cancer. 2019;10(3):697.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Carlo MI, Hakimi AA, Stewart GD, Bratslavsky G, Brugarolas J, Chen Y-B, et al. Familial kidney cancer: implications of new syndromes and molecular insights. Eur Urol. 2019;76(6):754–64.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Di Martino E, Tomlinson DC, Williams SV, Knowles MA. A place for precision medicine in bladder cancer: targeting the FGFRs. Future Oncol. 2016;12(19):2243–63.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Liu G, Chen T, Ding Z, Wang Y, Wei Y, Wei X. Inhibition of FGF-FGFR and VEGF-VEGFR signalling in cancer treatment. Cell Prolif. 2021;54(4): e13009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Krook MA, Reeser JW, Ernst G, Barker H, Wilberding M, Li G, et al. Fibroblast growth factor receptors in cancer: genetic alterations, diagnostics, therapeutic targets and mechanisms of resistance. Br J Cancer. 2021;124(5):880–92.

    Article  CAS  PubMed  Google Scholar 

  39. Santolla MF, Maggiolini M. The FGF/FGFR system in breast cancer: oncogenic features and therapeutic perspectives. Cancers (Basel). 2020;12(10):3029.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Katoh M. Fibroblast growth factor receptors as treatment targets in clinical oncology. Nat Rev Clin Oncol. 2019;16(2):105–22.

    Article  CAS  PubMed  Google Scholar 

  41. Babina IS, Turner NC. Advances and challenges in targeting FGFR signalling in cancer. Nat Rev Cancer. 2017;17(5):318–32.

    Article  CAS  PubMed  Google Scholar 

  42. Peng X, Hou P, Chen Y, Dai Y, Ji Y, Shen Y, et al. Preclinical evaluation of 3D185, a novel potent inhibitor of FGFR1/2/3 and CSF-1R, in FGFR-dependent and macrophage-dominant cancer models. J Exp Clin Cancer Res. 2019;38(1):1–16.

    Article  Google Scholar 

  43. Kwon W-A, Seo HK. Emerging agents for the treatment of metastatic urothelial cancer. Investig Clin Urol. 2021;62(3):243–55.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Kacew A, Sweis RF. FGFR3 alterations in the era of immunotherapy for urothelial bladder cancer. Front Immunol. 2020;11: 575258.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Robertson AG, Kim J, Al-Ahmadie H, Bellmunt J, Guo G, Cherniack AD, et al. Comprehensive molecular characterization of muscle-invasive bladder cancer. Cell. 2017;171(3):540-56.e25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Marangoni F, Zhakyp A, Corsini M, Geels SN, Carrizosa E, Thelen M, et al. Expansion of tumor-associated Treg cells upon disruption of a CTLA-4-dependent feedback loop. Cell. 2021;184(15):3998-4015.e19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Ren S, Xiong X, You H, Shen J, Zhou P. The combination of immune checkpoint blockade and angiogenesis inhibitors in the treatment of advanced non-small cell lung cancer. Front Immunol. 2021;12:2136.

    Article  Google Scholar 

  48. Zang J, Ye K, Fei Y, Zhang R, Chen H, Zhuang G. Immunotherapy in the treatment of urothelial bladder cancer: insights from single-cell Aaalysis. Front Oncol. 2021;11: 696716.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Khalaf K, Hana D, Chou JT-T, Singh C, Mackiewicz A, Kaczmarek M. Aspects of the tumor microenvironment involved in immune resistance and drug resistance. Front Immunol. 2021;12: 656364.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Peng M, Xiao D, Bu Y, Long J, Yang X, Lv S, et al. Novel combination therapies for the treatment of bladder cancer. Front Oncol. 2021;10: 539527.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Steelman LS, Chappell WH, Abrams SL, Kempf CR, Long J, Laidler P, et al. Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging. Aging (Albany N Y). 2011;3(3):192.

    CAS  Google Scholar 

  52. Zang J, Ye K, Fei Y, Zhang R, Chen H, Zhuang G. Immunotherapy in the treatment of urothelial bladder cancer: insights from single-cell analysis. Front Oncol. 2021;11.

  53. Tran L, Xiao JF, Agarwal N, Duex JE, Theodorescu D. Advances in bladder cancer biology and therapy. Nat Rev Cancer. 2021;21(2):104–21. https://doi.org/10.1038/s41568-020-00313-1.

    Article  CAS  PubMed  Google Scholar 

  54. Tang T, Huang X, Zhang G, Hong Z, Bai X, Liang T. Advantages of targeting the tumor immune microenvironment over blocking immune checkpoint in cancer immunotherapy. Signal Transduct Target Ther. 2021;6(1):72.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Mollica V, Rizzo A, Montironi R, Cheng L, Giunchi F, Schiavina R, et al. Current strategies and novel therapeutic approaches for metastatic urothelial carcinoma. Cancers (Basel). 2020;12(6):1449.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Wang L, Gong Y, Saci A, Szabo PM, Martini A, Necchi A, et al. Fibroblast growth factor receptor 3 alterations and response to PD-1/PD-L1 blockade in patients with metastatic urothelial cancer. Eur Urol. 2019;76(5):599–603.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Tang T, Huang X, Zhang G, Hong Z, Bai X, Liang T. Advantages of targeting the tumor immune microenvironment over blocking immune checkpoint in cancer immunotherapy. Signal Transduction Targeted Ther. 2021;6(1):1–13.

    Article  Google Scholar 

  58. Roche H. A study of atezolizumab in participants with locally advanced or metastatic urothelial bladder cancer (cohort 2). NLM identifier: NCT02108652 Available from: https://clinicaltrials.gov/ct2/show/NCT02108652. Accessed 19 May 2020.

  59. Moreno V, Loriot Y, Valderrama BP, Beato C, Vano Y-A, Fleming MT, et al. Does escalation results from phase Ib/II Norse study of erdafitinib (ERDA)+ PD-1 inhibitor JNJ-63723283 (cetrelimab [CET]) in patients (pts) with metastatic or locally advanced urothelial carcinoma (mUC) and selected fibroblast growth factor receptor (FGFR) gene alterations. 2020.

  60. Lee HW, Seo HK. Fibroblast growth factor inhibitors for treating locally advanced/metastatic bladder urothelial carcinomas via dual targeting of tumor-specific oncogenic signaling and the tumor immune microenvironment. Int J Mol Sci. 2021;22(17):9526.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Barrueto L, Caminero F, Cash L, Makris C, Lamichhane P, Deshmukh RR. Resistance to checkpoint inhibition in cancer immunotherapy. Transl Oncol. 2020;13(3): 100738.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Rosenberg JE, Gajate P, Morales-Barrera R, Lee J-L, Necchi A, Penel N, et al. Safety and efficacy of rogaratinib in combination with atezolizumab in cisplatin-ineligible patients (pts) with locally advanced or metastatic urothelial cancer (UC) and FGFR mRNA overexpression in the phase Ib/II FORT-2 study. J Clin Oncol. 2021;39(15_Suppl):4521.

    Article  Google Scholar 

  63. Smith KER, Hitron EE, Russler GA, Baumgarten DA, Bilen MA. Ramucirumab and docetaxel in patients with metastatic urothelial carcinoma harboring fibroblast growth factor receptor alterations: a case series and literature review. J Immunother Precis Oncol. 2020;3(1):23–6.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Pietzak EJ, Bagrodia A, Cha EK, Drill EN, Iyer G, Isharwal S, et al. Next-generation sequencing of nonmuscle invasive bladder cancer reveals potential biomarkers and rational therapeutic targets. Eur Urol. 2017;72(6):952–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Akanksha M, Sandhya S. Role of FGFR3 in urothelial carcinoma. Iran J Pathol. 2019;14(2):148–55. https://doi.org/10.30699/IJP.14.2.148

    Article  PubMed Central  Google Scholar 

  66. van Rhijn BW, Mertens LS, Mayr R, Bostrom PJ, Real FX, Zwarthoff EC, et al. FGFR3 mutation status and FGFR3 expression in a large bladder cancer cohort treated by radical cystectomy: implications for anti-FGFR3 treatment? Eur Urol. 2020;78(5):682–7.

    Article  PubMed  Google Scholar 

  67. Montironi R, Lopez-Beltran A, Cheng L. Editorial comment on: prediction of progression of non-muscle-invasive bladder cancer by WHO 1973 and 2004 grading and by FGFR3 mutation status: a prospective study. Eur Urol. 2008;54(4):843–4.

    Article  PubMed  Google Scholar 

  68. Van Rhijn BW, Van Der Kwast TH, Liu L, Fleshner NE, Bostrom PJ, Vis AN, et al. The FGFR3 mutation is related to favorable pT1 bladder cancer. J Urol. 2012;187(1):310–4.

    Article  PubMed  Google Scholar 

  69. Tan TZ, Rouanne M, Tan KT, Huang RY-J, Thiery J-P. Molecular subtypes of urothelial bladder cancer: results from a meta-cohort analysis of 2411 tumors. Eur Urol. 2019;75(3):423–32.

    Article  CAS  PubMed  Google Scholar 

  70. Seiler R, Ashab HAD, Erho N, van Rhijn BW, Winters B, Douglas J, et al. Impact of molecular subtypes in muscle-invasive bladder cancer on predicting response and survival after neoadjuvant chemotherapy. Eur Urol. 2017;72(4):544–54.

    Article  CAS  PubMed  Google Scholar 

  71. Sevillano Fernández E, Madurga de Lacalle R, Rodriguez Moreno JF, Barquín García A, Yagüe Fernández M, Navarro Alcaraz P, et al. Prognostic value and clinical significance of FGFR genomic alterations (GAs) in metastatic urothelial cancer patients. J Clin Med. 2022;11(15):4483.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine, SUNY Upstate Medical University, Syracuse, NY, USA

    Maroun Bou Zerdan

  2. Department of Urology, SUNY Upstate Medical University, Syracuse, NY, USA

    Gennady Bratslavsky & Joseph Jacob

  3. Foundation Medicine, Inc., Morrisville, NC, USA

    Jeffrey Ross & Richard Huang

  4. Department of Pathology, SUNY Upstate Medical University, Syracuse, NY, USA

    Jeffrey Ross

  5. Department of Urology, SUNY Upstate Medical University, Syracuse, NY, USA

    Jeffrey Ross

  6. Department of Hematology and Oncology, State University of New York, Upstate Medical University, 750 East Adams Street, Syracuse, NY, 13210-2375, USA

    Alina Basnet

Authors
  1. Maroun Bou Zerdan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gennady Bratslavsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joseph Jacob
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jeffrey Ross
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Richard Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alina Basnet
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alina Basnet.

Ethics declarations

Funding

No funding was received for the preparation of this article.

Conflicts of Interest/Competing Interests

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Maroun Bou Zerdan, Gennady Bratslavsky, Joseph Jacob, Jeffrey Ross, Richard Huang, and Alina Basnet have no conflicts of interests that are directly relevant to the content of this article.

Ethics Approval

The Western Institutional Review Board (Protocol No. 20152817) approved this retrospective database search.

Consent to Participate

Approval for this study, including a waiver of informed consent and HIPAA waiver of authorization, was obtained from the Western Institutional Review Board (protocol 20152817).

Consent for Publication

Not applicable.

Availability of Data and Material

The original contributions presented in the study are included in the article, further inquiries can be directed to the corresponding author/s. The data underlying this article were provided by Foundation Medicine under license, by permission. Data will be shared on request to the corresponding author with the permission of Foundation Medicine.

Code Availability

Not applicable.

Authors’ Contributions

JR, JJ, GB, and AB contributed to the conception and design of the study. RH and JR organized the database. RH performed the statistical analysis. MBZ wrote the first draft of the manuscript. RH and MBZ wrote sections of the manuscript. All authors contributed to the manuscript revision and read and approved the submitted version.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bou Zerdan, M., Bratslavsky, G., Jacob, J. et al. Urothelial Bladder Cancer: Genomic Alterations in Fibroblast Growth Factor Receptor. Mol Diagn Ther 27, 475–485 (2023). https://doi.org/10.1007/s40291-023-00647-0

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40291-023-00647-0

Search

Navigation