Single-Cell Exome Sequencing Reveals Single-Nucleotide Mutation Characteristics of a Kidney Tumor
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Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer and has very few mutations that are shared between different patients. To better understand the intratumoral genetics underlying mutations of ccRCC, we carried out single-cell exome sequencing on a ccRCC tumor and its adjacent kidney tissue. Our data indicate that this tumor was unlikely to have resulted from mutations in VHL and PBRM1. Quantitative population genetic analysis indicates that the tumor did not contain any significant clonal subpopulations and also showed that mutations that had different allele frequencies within the population also had different mutation spectrums. Analyses of these data allowed us to delineate a detailed intratumoral genetic landscape at a single-cell level. Our pilot study demonstrates that ccRCC may be more genetically complex than previously thought and provides information that can lead to new ways to investigate individual tumors, with the aim of developing more effective cellular targeted therapies.
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Rapid technological advances have enabled genome-wide profiling of RNA, DNA, protein, epigenetic modifications, chromatin accessibility, and other molecular events in single cells.
“rapid technological advances have enabled genome-wide profiling of RNA7–10, DNA11–17, protein18–21, epigenetic modifications22–26, chromatin accessibility27,28, and other molecular events29 in single cells.”
From Revealing the vectors of cellular identity with single-cell genomics (2016) · cites this paper as [13]
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Huss, W. J., Hu, Q., Glenn, S. T., Gangavarapu, K. J., Wang, J., Luce, J. D., Quinn, P. K., Brese, E. A., Zhan, F., Conroy, J. M., et al. (2018) · Human Heredity · doi:10.1159/000490506 · Cited by 8 · see citing works
Self-citation
- Authors
- Xu, X., Hou, Y., Yin, X., Bao, L., Tang, A., Song, L., Li, F., Tsang, S., Wu, K., Wu, H., He, W., Zeng, L., Xing, M., Wu, R., Jiang, H., Liu, X., Cao, D., Guo, G., Hu, X., Gui, Y., Li, Z., Xie, W., Sun, X., Shi, M., Cai, Z., Wang, B., Zhong, M., Li, J., Lu, Z., Gu, N., Zhang, X., Goodman, L., Bolund, L., Wang, J., Yang, H., Kristiansen, K., Dean, M., Li, Y., & Wang, J.
- Affiliations
- BGI Group (China) (CN)
- Shenzhen University (CN)
- Peking University Shenzhen Hospital (CN)
- State Key Laboratory of Digital Medical Engineering (CN)
- Corresponding author
- Dean, Michael
- Li, Yingrui
- Wang, Jun
- ORCID
- Xu, Xun
- Hou, Yong
- Yin, Xuyang
- Bao, Li
- Tang, Aifa
- Li, Fuqiang
- Wu, Kui
- Wu, Hanjie
- He, Weiming
- Zeng, Liang
- Wu, Renhua
- Jiang, Hui
- Liu, Xiao
- Cao, Dandan
- Guo, Guangwu
- Gui, Yaoting
- Li, Zesong
- Shi, Min
- Cai, Zhiming
- Wang, Bin
- Lu, Zuhong
- Gu, Ning
- Zhang, Xiuqing
- Goodman, Laurie
- Bolund, Lars
- Wang, Jian
- Kristiansen, Karsten
- Dean, Michael
- Wang, Jun
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2012-03
- Volume
- 148
- Issue
- 5
- Pages
- 886-895
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC7458411
- OpenAlex
- W2009569945
- Cited by
- 667
- References
- 56
- Citations by year
- 2026: 4 · 2025: 15 · 2024: 15 · 2023: 26 · 2022: 49 · 2021: 31 · 2020: 42 · 2019: 41 · 2018: 61 · 2017: 58 · 2016: 50 · 2015: 56 · 2014: 79 · 2013: 86 · 2012: 53
- FWCI
- 28.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (R21AA022707)
- National Cancer Institute (ZIABC011301, ZIABC011300)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Renal cell carcinoma treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- clear cell renal cell carcinoma, intratumoral heterogeneity, point mutations, clonal subpopulations, VHL, PBRM1, allele frequency, tumor evolution, targeted therapy
- MeSH terms
- Carcinoma, Renal Cell, DNA-Binding Proteins, Gene Frequency, Humans, Kidney Neoplasms, Male, Middle Aged, Mutation, Nuclear Proteins, Phylogeny, Pilot Projects, Transcription Factors, Principal Component Analysis, Von Hippel-Lindau Tumor Suppressor Protein, Single-Cell Analysis, Exome
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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