Single-Cell Sequencing in Genitourinary Malignancies
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
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Neal Murphy, Pratik Shah, Andrew Shih, Houman Khalili, Anthony Liew, Xinhua Zhu, and Annette Lee
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 N. Murphy (*) Department of Medicine, Long Island Jewish Medical Center, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New Hyde Park, NY, USA e-mail: [email protected] P. Shah Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA A. Shih · H. Khalili · A. Liew · A. Lee Feinstein Institute for Medical Research, Manhasset, NY, USA X. Zhu Northwell Health Cancer Institute, Lake Success, NY, USA
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 precisionbased care. Keywords
Single-cell sequencing · Next generation sequencing · Renal cell carcinoma · Bladder cancer · Prostate cancer · Tumor heterogeneity · Tumor microenvironment · Cancer stem cells · Circulating tumor cells · Clonal evolution · Chemotherapy resistance
# Springer Nature Singapore Pte Ltd. 2020 B. Yu et al. (eds.), Single-cell Sequencing and Methylation, Advances in Experimental Medicine and Biology 1255, https://doi.org/10.1007/978-981-15-4494-1_13
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Introduction
Genitourinary (GU) malignancies, including prostate, bladder, and renal cell carcinoma (RCC), are associated with significant morbidity and mortality in the United States, and individually
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