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Single-Cell Sequencing in Genitourinary Malignancies

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Single-cell Sequencing and Methylation

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1255))

Abstract

Single-cell sequencing (SCS) is a powerful new tool that applies Next Generation Sequencing at the cellular level. SCS has revolutionized our understanding of tumor heterogeneity and the tumor microenvironment, immune infiltration, cancer stem cells (CSCs), circulating tumor cells (CTCs), and clonal evolution. The following chapter highlights the current literature on SCS in genitourinary (GU) malignancies and discusses future applications of SCS technology. The renal cell carcinoma (RCC) section highlights the use of SCS in characterizing the initial cells driving tumorigenesis, the intercellular mutational landscape of RCC, intratumoral heterogeneity (ITH) between primary and metastatic lesions, and genes driving RCC cancer stem cells (CSCs). The bladder cancer section will also illustrate molecular drivers of bladder cancer stem cells (BCSCs), SCS use in reconstructing tumor developmental history and underlying subclones, and understanding the effect of cisplatin on intratumoral heterogeneity in vitro and potential mechanisms behind platinum resistance. The final section featuring prostate cancer will discuss how SCS can be used to identify the cellular origins of benign prostatic hyperplasia and prostate cancer, the plasticity and heterogeneity of prostate cancer cells with regard to androgen dependence, and the use of SCS in CTCs to understand chemotherapy resistance and gene expression changes after androgen deprivation therapy (ADT). The studies listed in this chapter illustrate many translational applications of SCS in GU malignancies, including diagnostic, prognostic, and treatment-related approaches. The ability of SCS to resolve intratumor heterogeneity and better define the genomic landscape of tumors and CTCs will be fundamental in the new era of precision-based care.

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References

  1. Common cancer sites—cancer stat facts. In: SEER [Internet]. [cited 16 Sep 2019]. https://seer.cancer.gov/statfacts/html/common.html

  2. Morash M, Mitchell H, Beltran H, Elemento O, Pathak J (2018) The role of next-generation sequencing in precision medicine: a review of outcomes in oncology. J Pers Med 8(3):pii: E30. https://doi.org/10.3390/jpm8030030

    Article  Google Scholar 

  3. Young MD, Mitchell TJ, Vieira Braga FA, Tran MGB, Stewart BJ, Ferdinand JR et al (2018) Single-cell transcriptomes from human kidneys reveal the cellular identity of renal tumors. Science 361:594–599

    Article  CAS  Google Scholar 

  4. Xu X, Hou Y, Yin X, Bao L, Tang A, Song L et al (2012) Single-cell exome sequencing reveals single-nucleotide mutation characteristics of a kidney tumor. Cell 148:886–895

    Article  CAS  Google Scholar 

  5. Hou Y, Song L, Zhu P, Zhang B, Tao Y, Xu X et al (2012) Single-cell exome sequencing and monoclonal evolution of a JAK2-negative myeloproliferative neoplasm. Cell 148:873–885

    Article  CAS  Google Scholar 

  6. Kim K-T, Lee HW, Lee H-O, Song HJ, Jeong DE, Shin S et al (2016) Application of single-cell RNA sequencing in optimizing a combinatorial therapeutic strategy in metastatic renal cell carcinoma. Genome Biol 17:80

    Article  Google Scholar 

  7. Florek M, Haase M, Marzesco A-M, Freund D, Ehninger G, Huttner WB et al (2005) Prominin-1/CD133, a neural and hematopoietic stem cell marker, is expressed in adult human differentiated cells and certain types of kidney cancer. Cell Tissue Res 319:15–26

    Article  CAS  Google Scholar 

  8. Li C, Wu S, Yang Z, Zhang X, Zheng Q, Lin L et al (2017) Single-cell exome sequencing identifies mutations in KCP, LOC440040, and LOC440563 as drivers in renal cell carcinoma stem cells. Cell Res 27:590–593

    Article  CAS  Google Scholar 

  9. Chen A, Fu G, Xu Z, Sun Y, Chen X, Cheng KS et al (2018) Detection of urothelial bladder carcinoma via microfluidic immunoassay and single-cell DNA copy-number alteration analysis of captured urinary-exfoliated tumor cells. Cancer Res 78:4073–4085

    Article  CAS  Google Scholar 

  10. Yang Z, Li C, Fan Z, Liu H, Zhang X, Cai Z et al (2017) Single-cell sequencing reveals variants in ARID1A, GPRC5A and MLL2 driving self-renewal of human bladder cancer stem cells. Eur Urol 71:8–12

    Article  Google Scholar 

  11. Chan KS, Espinosa I, Chao M, Wong D, Ailles L, Diehn M et al (2009) Identification, molecular characterization, clinical prognosis, and therapeutic targeting of human bladder tumor-initiating cells. Proc Natl Acad Sci U S A 106:14016–14021

    Article  CAS  Google Scholar 

  12. Li Y, Xu X, Song L, Hou Y, Li Z, Tsang S et al (2012) Single-cell sequencing analysis characterizes common and cell-lineage-specific mutations in a muscle-invasive bladder cancer. Gigascience 1:12

    Article  Google Scholar 

  13. Zhang X, Zhang M, Hou Y, Xu L, Li W, Zou Z et al (2016) Single-cell analyses of transcriptional heterogeneity in squamous cell carcinoma of urinary bladder. Oncotarget 7:66069–66076

    Article  Google Scholar 

  14. Tanaka N, Katayama S, Reddy A, Nishimura K, Niwa N, Hongo H et al (2018) Single-cell RNA-seq analysis reveals the platinum resistance gene COX7B and the surrogate marker CD63. Cancer Med 7:6193–6204

    Article  CAS  Google Scholar 

  15. Henry GH, Malewska A, Joseph DB, Malladi VS, Lee J, Torrealba J et al (2018) A cellular anatomy of the normal adult human prostate and prostatic urethra. Cell Rep 25:3530–3542.e5

    Article  CAS  Google Scholar 

  16. Horning AM, Wang Y, Lin C-K, Louie AD, Jadhav RR, Hung C-N et al (2018) Single-cell RNA-seq reveals a subpopulation of prostate cancer cells with enhanced cell-cycle-related transcription and attenuated androgen response. Cancer Res 78:853–864

    Article  CAS  Google Scholar 

  17. Cann GM, Gulzar ZG, Cooper S, Li R, Luo S, Tat M et al (2012) mRNA-Seq of single prostate cancer circulating tumor cells reveals recapitulation of gene expression and pathways found in prostate cancer. PLoS One 7:e49144

    Article  CAS  Google Scholar 

  18. Lohr JG, Adalsteinsson VA, Cibulskis K, Choudhury AD, Rosenberg M, Cruz-Gordillo P et al (2014) Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer. Nat Biotechnol 32:479–484

    Article  CAS  Google Scholar 

  19. Dago AE, Stepansky A, Carlsson A, Luttgen M, Kendall J, Baslan T et al (2014) Rapid phenotypic and genomic change in response to therapeutic pressure in prostate cancer inferred by high content analysis of single circulating tumor cells. PLoS One 9:e101777

    Article  Google Scholar 

  20. Navin N, Kendall J, Troge J, Andrews P, Rodgers L, McIndoo J et al (2011) Tumour evolution inferred by single-cell sequencing. Nature 472:90–94

    Article  CAS  Google Scholar 

  21. Baslan T, Kendall J, Rodgers L, Cox H, Riggs M, Stepansky A et al (2012) Genome-wide copy number analysis of single cells. Nat Protoc 7:1024–1041

    Article  CAS  Google Scholar 

  22. Li B, Simon MC (2013) Molecular pathways: targeting MYC-induced metabolic reprogramming and oncogenic stress in cancer. Clin Cancer Res 19:5835–5841

    Article  CAS  Google Scholar 

  23. Armstrong AJ, Halabi S, Luo J, Nanus DM, Giannakakou P, Szmulewitz RZ et al (2019) Prospective multicenter validation of androgen receptor splice variant 7 and hormone therapy resistance in high-risk castration-resistant prostate cancer: the PROPHECY study. J Clin Oncol 37:1120–1129

    Article  CAS  Google Scholar 

  24. Miyamoto DT, Zheng Y, Wittner BS, Lee RJ, Zhu H, Broderick KT et al (2015) RNA-Seq of single prostate CTCs implicates noncanonical Wnt signaling in antiandrogen resistance. Science 349:1351–1356

    Article  CAS  Google Scholar 

  25. Trepel J, Mollapour M, Giaccone G, Neckers L (2010) Targeting the dynamic HSP90 complex in cancer. Nat Rev Cancer 10:537–549

    Article  CAS  Google Scholar 

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Correspondence to Neal Murphy .

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Murphy, N. et al. (2020). Single-Cell Sequencing in Genitourinary Malignancies. In: Yu, B., Zhang, J., Zeng, Y., Li, L., Wang, X. (eds) Single-cell Sequencing and Methylation. Advances in Experimental Medicine and Biology, vol 1255. Springer, Singapore. https://doi.org/10.1007/978-981-15-4494-1_13

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