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Bladder Cancer Genomics: Indications for Sequencing and Diagnostic Implications

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Comprehensive Diagnostic Approach to Bladder Cancer

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Abstract

It has been long understood that bladder cancer harbors specific genomic and copy number alterations. More recently, increased access by way of availability and reduced costs of next-generation sequencing has resulted in an improved understanding of the molecular biology of bladder cancer. Data from genomic sequencing yield prognostic information that may aid in the decision to pursue aggressive therapies, as well as predictive information regarding response to treatments such as intravesical Bacillus Calmette-Guerin (BCG) and systemic chemotherapy. Genomic sequencing also provides data on targetable alterations that can bring novel agents from the laboratory to clinical trials. As the material for deep and broad genomic sequencing is expanded to include both plasma and urine, new avenues to screen and monitor disease are becoming available. While current guidelines recommend sequencing only for patients with advanced and metastatic disease, currently active clinical trials may expand these indications in the near future.

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References

  1. Clinical N, Guidelines P, Guidelines N. Non-small cell lung. 2021.

    Google Scholar 

  2. Alexandrov LB, Nik-Zainal S, Wedge DC, et al. Signatures of mutational processes in human cancer. Nature. 2013;500(7463):415–21. https://doi.org/10.1038/nature12477.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Alekseyev YO, Fazeli R, Yang S, et al. A next-generation sequencing primer—how does it work and what can it do? Acad Pathol. 2018;5:1–11. https://doi.org/10.1177/2374289518766521.

    Article  Google Scholar 

  4. Sims D, Sudbery I, Ilott NE, Heger A, Ponting CP. Sequencing depth and coverage: key considerations in genomic analyses. Nat Rev Genet. 2014;15(2):121–32. https://doi.org/10.1038/nrg3642.

    Article  CAS  PubMed  Google Scholar 

  5. Ptashkin RN, Mandelker DL, Coombs CC, et al. Prevalence of clonal hematopoiesis mutations in tumor-only clinical genomic profiling of solid tumors. JAMA Oncol. 2018. https://doi.org/10.1001/jamaoncol.2018.2297.

  6. Parikh K, Huether R, White K, et al. Tumor mutational burden from tumor-only sequencing compared with germline subtraction from paired tumor and normal specimens. JAMA Netw Open. 2020;3(2):e200202. https://doi.org/10.1001/jamanetworkopen.2020.0202.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Chakravarty D, Gao J, Phillips S, et al. OncoKB: a precision oncology knowledge base. JCO Precis Oncol. 2017. https://doi.org/10.1200/po.17.00011.

  8. Faltas BM, Prandi D, Tagawa ST, et al. Clonal evolution of chemotherapy-resistant urothelial carcinoma. Nat Genet. 2016. https://doi.org/10.1038/ng.3692.

  9. Cancer T, Atlas G. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature. 2014;507(7492):315–22. https://doi.org/10.1038/nature12965.

    Article  CAS  Google Scholar 

  10. Robertson AG, Kim J, Al-Ahmadie H, et al. Comprehensive molecular characterization of muscle-invasive bladder cancer. Cell. 2017;171(3):540–556.e25. https://doi.org/10.1016/j.cell.2017.09.007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Lawrence MS, Stojanov P, Polak P, et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature. 2013;499(7457):214–8. https://doi.org/10.1038/nature12213.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Li R, Du Y, Chen Z, et al. Macroscopic somatic clonal expansion in morphologically normal human urothelium. Science (80- ). 2020;370(6512):82–9.

    Article  CAS  Google Scholar 

  13. Lawson ARJ, Abascal F, Coorens THH, et al. Extensive heterogeneity in somatic mutation and selection in the human bladder. Science (80- ). 2020;370(6512):75–82.

    Article  CAS  Google Scholar 

  14. Kamoun A, de Reyniès A, Allory Y, et al. A consensus molecular classification of muscle-invasive bladder cancer [Formula presented]. Eur Urol. 2020;77(4):420–33. https://doi.org/10.1016/j.eururo.2019.09.006.

    Article  PubMed  Google Scholar 

  15. Seiler R, Ashab HAD, Erho N, 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 

  16. Van Allen EM, Mouw KW, Kim P, et al. Somatic ERCC2 mutations correlate with cisplatin sensitivity in muscle-invasive urothelial carcinoma. Cancer Discov. 2014;4(10):1140–53. https://doi.org/10.1158/2159-8290.CD-14-0623.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Li Q, Damish AW, Frazier Z, et al. ERCC2 helicase domain mutations confer nucleotide excision repair deficiency and drive cisplatin sensitivity in muscle-invasive bladder cancer. Clin Cancer Res. 2019;25(3):977–88. https://doi.org/10.1158/1078-0432.CCR-18-1001.

    Article  CAS  PubMed  Google Scholar 

  18. Pietzak EJ, Zabor EC, Bagrodia A, et al. Genomic differences between “primary” and “secondary” muscle-invasive bladder cancer as a basis for disparate outcomes to cisplatin-based neoadjuvant chemotherapy. Eur Urol. 2019;75(2):231–9. https://doi.org/10.1016/j.eururo.2018.09.002.

    Article  PubMed  Google Scholar 

  19. Teo MY, Mota JM, Whiting KA, et al. Fibroblast growth factor receptor 3 alteration status is associated with differential sensitivity to platinum-based chemotherapy in locally advanced and metastatic urothelial carcinoma. Eur Urol. 2020;78(6):907–15. https://doi.org/10.1016/j.eururo.2020.07.018.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Iyer G, Al-Ahmadie H, Schultz N, et al. Prevalence and co-occurrence of actionable genomic alterations in high-grade bladder cancer. J Clin Oncol. 2013;31(25):3133–40. https://doi.org/10.1200/JCO.2012.46.5740.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Al-Ahmadie HA, Iyer G, Lee BH, et al. Frequent somatic CDH1 loss-of-function mutations in plasmacytoid variant bladder cancer. Nat Genet. 2016;48(4):356–8. https://doi.org/10.1038/ng.3503.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Chang MT, Penson A, Desai NB, et al. Small-cell carcinomas of the bladder and lung are characterized by a convergent but distinct pathogenesis. Clin Cancer Res. 2018;24(8):1965–73. https://doi.org/10.1158/1078-0432.CCR-17-2655.

    Article  CAS  PubMed  Google Scholar 

  23. Hedegaard J, Lamy P, Nordentoft I, et al. Comprehensive transcriptional analysis of early-stage urothelial carcinoma. Cancer Cell. 2016;30(1):27–42. https://doi.org/10.1016/J.CCELL.2016.05.004.

    Article  CAS  PubMed  Google Scholar 

  24. Hurst CD, Alder O, Platt FM, et al. Genomic subtypes of non-invasive bladder cancer with distinct metabolic profile and female gender bias in KDM6A mutation frequency. Cancer Cell. 2017;32(5):701–715.e7. https://doi.org/10.1016/j.ccell.2017.08.005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Patschan O, Sjödahl G, Chebil G, et al. A molecular pathologic framework for risk stratification of stage T1 urothelial carcinoma. Eur Urol. 2015; https://doi.org/10.1016/j.eururo.2015.02.021.

  26. Robertson AG, Groeneveld CS, Jordan B, et al. Identification of differential tumor subtypes of T1 bladder cancer. Eur Urol. 2020. https://doi.org/10.1016/j.eururo.2020.06.048.

  27. Pietzak EJ, Bagrodia A, Cha EK, et al. Next-generation sequencing of nonmuscle invasive bladder cancer reveals potential biomarkers and rational therapeutic targets. Eur Urol. 2017;72(6):952–9. https://doi.org/10.1016/j.eururo.2017.05.032.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Nassar AH, Umeton R, Kim J, et al. Mutational analysis of 472 urothelial carcinoma across grades and anatomic sites. Clin Cancer Res. 2019;25(8):2458–70. https://doi.org/10.1158/1078-0432.CCR-18-3147.

    Article  PubMed  Google Scholar 

  29. Bellmunt J, Kim J, Reardon B, et al. Genomic predictors of good outcome, recurrence, or progression in high-grade T1 non–muscle-invasive bladder cancer. Cancer Res. 2020;80(20):4476–86. https://doi.org/10.1158/0008-5472.CAN-20-0977.

    Article  CAS  PubMed  Google Scholar 

  30. Winters BR, De Sarkar N, Arora S, et al. Genomic distinctions between metastatic lower and upper tract urothelial carcinoma revealed through rapid autopsy. JCI Insight. 2019;4(13). https://doi.org/10.1172/jci.insight.128728.

  31. Loriot Y, Necchi A, Park SH, et al. Erdafitinib in locally advanced or metastatic urothelial carcinoma. N Engl J Med. 2019;381(4):338–48. https://doi.org/10.1056/nejmoa1817323.

    Article  CAS  PubMed  Google Scholar 

  32. Mucci LA, Hjelmborg JB, Harris JR, et al. Familial risk and heritability of cancer among twins in nordic countries. JAMA. 2016;315(1):68–76. https://doi.org/10.1001/jama.2015.17703.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Nassar AH, Abou Alaiwi S, AlDubayan SH, et al. Prevalence of pathogenic germline cancer risk variants in high-risk urothelial carcinoma. Genet Med. 2019;0(0):1–10. https://doi.org/10.1038/s41436-019-0720-x.

    Article  CAS  Google Scholar 

  34. Carlo MI, Ravichandran V, Srinavasan P, et al. Cancer susceptibility mutations in patients with urothelial malignancies. J Clin Oncol. 2020;38(5):406–14. https://doi.org/10.1200/JCO.19.01395.

    Article  CAS  PubMed  Google Scholar 

  35. Kouba E, Lopez-Beltran A, Montironi R, et al. Liquid biopsy in the clinical management of bladder cancer: current status and future developments. Expert Rev Mol Diagn. 2019;00(00):1–10. https://doi.org/10.1080/14737159.2019.1680284.

    Article  CAS  Google Scholar 

  36. Vandekerkhove G, Lavoie J, Annala M, et al. Plasma ctDNA is a tumor tissue surrogate and enables clinical-genomic stratification of metastatic bladder cancer. Nat Commun. 2021:1–12. https://doi.org/10.1038/s41467-020-20493-6.

  37. Christensen E, Birkenkamp-Demtröder K, Sethi H, et al. Early detection of metastatic relapse and monitoring of therapeutic efficacy by ultra-deep sequencing of plasma cell-free DNA in patients with urothelial bladder carcinoma. J Clin Oncol. 2019;37(18):1547–57. https://doi.org/10.1200/JCO.18.02052.

    Article  CAS  PubMed  Google Scholar 

  38. Dudley JC, Schroers-Martin J, Lazzareschi DV, et al. Detection and surveillance of bladder cancer using urine tumor DNA. Cancer Discov. 2019;9(4):500–9. https://doi.org/10.1158/2159-8290.CD-18-0825.

    Article  CAS  PubMed  Google Scholar 

  39. Patel KM, van der Vos KE, Smith CG, et al. Association of plasma and urinary mutant DNA with clinical outcomes in muscle invasive bladder cancer. Sci Rep. 2017;7(1):5554. https://doi.org/10.1038/s41598-017-05623-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Flaig TW. NCCN guidelines updates: management of muscle-invasive bladder cancer. J Natl Compr Cancer Netw. 2019;17(5.5):591–3.

    CAS  Google Scholar 

  41. Chang Sam S, Boorjian SA, Chou R, et al. Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO guideline. J Urol. 2016;196(4):1021–9.

    Article  CAS  PubMed  Google Scholar 

  42. Chang SS, Bochner BH, Chou R, et al. Treatment of non-metastatic muscle-invasive bladder cancer: AUA/ASCO/ASTRO/SUO guideline (Amended 2020). 2020.

    Google Scholar 

  43. Wicklund CAL, Duquette DA, Swanson AL. Clinical genetic counselors: an asset in the era of precision medicine. Am J Med Genet Part C Semin Med Genet. 2018;178(1):63–7. https://doi.org/10.1002/ajmg.c.31605.

    Article  PubMed  Google Scholar 

  44. Jacobs MF, Milliron KJ. Genetic counseling and previvorship in patients with urologic malignancies. Curr Opin Urol. 2019;29(4):371–7. https://doi.org/10.1097/MOU.0000000000000638.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Andrew T. Lenis & Eugene J. Pietzak

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  1. Andrew T. Lenis
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  2. Eugene J. Pietzak
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Correspondence to Andrew T. Lenis .

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Editors and Affiliations

  1. Department of Urology, Lineberger Comprehensive Cancer Center & University of North Carolina, Chapel Hill, NC, USA

    Marc A. Bjurlin

  2. Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Richard S. Matulewicz

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Lenis, A.T., Pietzak, E.J. (2021). Bladder Cancer Genomics: Indications for Sequencing and Diagnostic Implications. In: Bjurlin, M.A., Matulewicz, R.S. (eds) Comprehensive Diagnostic Approach to Bladder Cancer. Springer, Cham. https://doi.org/10.1007/978-3-030-82048-0_11

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  • DOI: https://doi.org/10.1007/978-3-030-82048-0_11

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