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Genomic classification and risk stratification of bladder cancer

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Abstract

Bladder cancer is the fourth most common cancer in men and fifth most common overall. The use of next-generation sequencing (NGS) approaches is crucial to precisely characterize the molecular defects of tumors, and this information could be combined with other clinical data, such as tumor histology and TNM staging, with the goal of precise tumor classification. In many settings, targeted NGS is evaluated in patients with first- and second-line metastatic cancer. Yet, in the decade to come we anticipate increased application of precision oncology at all stages of bladder cancer with the aim of customizing cancer treatment. Here, we review the genomic and transcriptomic features associated with risk stratification in bladder cancer and summarize the current efforts for precision oncology in localized urothelial carcinomas.

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References

  1. Howlader NNA, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA. SEER Cancer Statistics Review, National Cancer Institute. Bethesda, MD

  2. Chang SS, Boorjian SA, Chou R et al (2016) Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO guideline. J Urol 196:1021–1029

    Article  PubMed  Google Scholar 

  3. Clark PE, Spiess PE, Agarwal N et al (2016) NCCN guidelines insights: bladder cancer, Version 2.2016. J Natl Compr Canc Netw 14:1213–1224

    Article  PubMed  PubMed Central  Google Scholar 

  4. Glaser AP, Fantini D, Shilatifard A et al (2017) The evolving genomic landscape of urothelial carcinoma. Nat Rev Urol 14:215–229

    Article  CAS  PubMed  Google Scholar 

  5. Babjuk M, Bohle A, Burger M et al (2017) EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2016. Eur Urol 71:447–461

    Article  PubMed  Google Scholar 

  6. Kirkali Z, Chan T, Manoharan M et al (2005) Bladder cancer: epidemiology, staging and grading, and diagnosis. Urology 66:4–34

    Article  PubMed  Google Scholar 

  7. Sylvester RJ, van der Meijden AP, Oosterlinck W et al (2006) Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur Urol 49:466–477 (discussion 475–467)

    Article  PubMed  Google Scholar 

  8. Hurst CD, Alder O, Platt FM et al (2017) Genomic subtypes of non-invasive bladder cancer with distinct metabolic profile and female gender bias in KDM6A mutation frequency. Cancer Cell 32:701–715.e707

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Meeks JJ, Lerner SP (2017) Molecular landscape of non-muscle invasive bladder cancer. Cancer Cell 32:550–551

    Article  CAS  PubMed  Google Scholar 

  10. Pal SK, Rosenberg JE, Hoffman-Censits JH et al (2018) Efficacy of BGJ398, a fibroblast growth factor receptor 1–3 inhibitor, in patients with previously treated advanced urothelial carcinoma with FGFR3 alterations. Cancer Discov 8:812–821

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hahn NM, Bivalacqua TJ, Ross AE et al (2016) A phase II trial of dovitinib in BCG-unresponsive urothelial carcinoma with FGFR3 mutations or overexpression: Hoosier Cancer Research Network Trial HCRN 12-157. Clin Cancer Res 23(12):3003–3011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hedegaard J, Lamy P, Nordentoft I et al (2016) Comprehensive transcriptional analysis of early-stage urothelial carcinoma. Cancer Cell 30:27–42

    Article  CAS  PubMed  Google Scholar 

  13. Sjodahl G, Lauss M, Lovgren K et al (2012) A molecular taxonomy for urothelial carcinoma. Clin Cancer Res 18:3377–3386

    Article  CAS  PubMed  Google Scholar 

  14. Meeks JJ, Carneiro BA, Pai SG et al (2016) Genomic characterization of high-risk non-muscle invasive bladder cancer. Oncotarget 7(46):75176

    Article  PubMed  PubMed Central  Google Scholar 

  15. Patschan O, Sjodahl G, Chebil G et al (2015) A molecular pathologic framework for risk stratification of stage T1 urothelial carcinoma. Eur Urol 68:824–832 (discussion 835–826)

    Article  CAS  PubMed  Google Scholar 

  16. Kim YJ, Ha YS, Kim SK et al (2010) Gene signatures for the prediction of response to Bacillus Calmette-Guerin immunotherapy in primary pT1 bladder cancers. Clin Cancer Res 16:2131–2137

    Article  CAS  PubMed  Google Scholar 

  17. Warrick JI, Hovelson DH, Amin A et al (2015) Tumor evolution and progression in multifocal and paired non-invasive/invasive urothelial carcinoma. Virchows Arch 466:297–311

    Article  CAS  PubMed  Google Scholar 

  18. Riaz N, Havel JJ, Makarov V et al (2017) Tumor and microenvironment evolution during immunotherapy with nivolumab. Cell 171(934–949):e915

    Google Scholar 

  19. Robertson AG, Kim J, Al-Ahmadie H et al (2017) Comprehensive molecular characterization of muscle-invasive bladder cancer. Cell 171(3):540–556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Cancer Genome Atlas Research N (2014) Comprehensive molecular characterization of urothelial bladder carcinoma. Nature 507:315–322

    Article  CAS  Google Scholar 

  21. Alexandrov LB, Nik-Zainal S, Wedge DC et al (2013) Signatures of mutational processes in human cancer. Nature 500:415–421

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. mutSignatures: Decipher Mutational Signatures from Somatic Mutational Catalogs

  23. Fantini D, Seiler R, Meeks JJ (2018) Molecular footprints of muscle-invasive bladder cancer in smoking and non-smoking patients. Urol Oncol

  24. Glaser AP, Fantini D, Rimar KJ et al (2017) APOBEC-Mediated Mutagenesis In Urothelial Carcinoma Is Associated With Improved Survival, Mutations In DNA Damage Response Genes, And Immune Response. bioRxiv

  25. Fantini D, Glaser AP, Rimar KJ et al (2018) A Carcinogen-induced mouse model recapitulates the molecular alterations of human muscle invasive bladder cancer. Oncogene 37:1911–1925

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wang L, Zhao Z, Ozark PA et al (2018) Resetting the epigenetic balance of Polycomb and COMPASS function at enhancers for cancer therapy. Nat Med 24:758–769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Rimar KJ, Tran PT, Matulewicz RS et al (2017) The emerging role of homologous recombination repair and PARP inhibitors in genitourinary malignancies. Cancer 123:1912–1924

    Article  CAS  PubMed  Google Scholar 

  28. Van Allen EM, Mouw KW, Kim P et al (2014) Somatic ERCC2 mutations correlate with cisplatin sensitivity in muscle-invasive urothelial carcinoma. Cancer Discov 4:1140–1153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Plimack ER, Dunbrack RL, Brennan TA et al (2015) Defects in DNA repair genes predict response to neoadjuvant cisplatin-based chemotherapy in muscle-invasive bladder cancer. Eur Urol 68:959–967

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Liu D, Plimack ER, Hoffman-Censits J et al (2016) Clinical validation of chemotherapy response biomarker ERCC2 in muscle-invasive urothelial bladder carcinoma. JAMA Oncol 2:1094–1096

    Article  PubMed  PubMed Central  Google Scholar 

  31. Felsenstein KM, Theodorescu D (2018) Precision medicine for urothelial bladder cancer: update on tumour genomics and immunotherapy. Nat Rev Urol 15:92–111

    Article  CAS  PubMed  Google Scholar 

  32. Teo MY, Seier K, Ostrovnaya I et al (2018) Alterations in DNA damage response and repair genes as potential marker of clinical benefit from PD-1/PD-l1 blockade in advanced urothelial cancers. J Clin Oncol 36:1685–1694

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Damrauer JS, Hoadley KA, Chism DD et al (2014) Intrinsic subtypes of high-grade bladder cancer reflect the hallmarks of breast cancer biology. Proc Natl Acad Sci USA 111:3110–3115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Kardos J, Chai S, Mose LE et al (2016) Claudin-low bladder tumors are immune infiltrated and actively immune suppressed. JCI Insight 1:e85902

    Article  PubMed  PubMed Central  Google Scholar 

  35. Sjodahl G, Eriksson P, Lovgren K et al (2018) Discordant molecular subtype classification in the basal-squamous subtype of bladder tumors and matched lymph-node metastases. Modern Pathol

  36. Sjodahl G, Eriksson P, Liedberg F et al (2017) Molecular classification of urothelial carcinoma: global mRNA classification versus tumour-cell phenotype classification. J Pathol 242:113–125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Marzouka NA, Eriksson P, Rovira C et al (2018) A validation and extended description of the Lund taxonomy for urothelial carcinoma using the TCGA cohort. Sci Rep 8:3737

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Mariathasan S, Turley SJ, Nickles D et al (2018) TGFbeta attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature 554:544–548

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Seiler R, Ashab HAD, Erho N et al (2017) Impact of molecular subtypes in muscle-invasive bladder cancer on predicting response and survival after neoadjuvant chemotherapy. Eur Urol 72:544–554

    Article  CAS  PubMed  Google Scholar 

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Funding

JJM is supported by Grant BX003692 and the John P. Hanson Foundation for Cancer Research at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

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Authors and Affiliations

  1. Department of Urology, Feinberg School of Medicine, Chicago, IL, USA

    Damiano Fantini & Joshua J. Meeks

  2. Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Chicago, IL, USA

    Damiano Fantini & Joshua J. Meeks

  3. Robert H. Lurie Cancer Center, Chicago, IL, USA

    Damiano Fantini & Joshua J. Meeks

  4. Jesse Brown VA Medical Center, Chicago, IL, USA

    Joshua J. Meeks

Authors
  1. Damiano Fantini
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  2. Joshua J. Meeks
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Contributions

Fantini- data collection and management, manuscript writing/editing. Meeks- data collection and management, manuscript writing/editing

Corresponding author

Correspondence to Joshua J. Meeks.

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Ethical statements

All research involving human subjects should refer back to primary studies.

Conflicts of interest

JJM is a consultant for AstraZeneca and Ferring and receives research funding from Epizyme, NextCure, Abbvie and Tesaro.

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Cite this article

Fantini, D., Meeks, J.J. Genomic classification and risk stratification of bladder cancer. World J Urol 37, 1751–1757 (2019). https://doi.org/10.1007/s00345-018-2558-2

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  • DOI: https://doi.org/10.1007/s00345-018-2558-2

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