Zesong Li, Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People’s Hospital, First Affiliated Hospital of Shenzhen University, China
Shirly Tsang, BioMatrix, United States
Fugiang Li, BGI-Shenzhen, China
Kate McGee, Cancer and Inflammation Program, National Cancer Institute at Frederick, United States
Kui Wu, BGI-Shenzhen, China
Hanjie Wu, BGI-Shenzhen, China
Xiaofei Ye, BGI-Shenzhen, China
Guibo Li, BGI-Shenzhen, China
Linlin Wang, BGI-Shenzhen, China
Bo Zhang, BGI-Shenzhen
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Jie Liang, BGI-Shenzhen, China
Wei Xie, BGI-Shenzhen, China
Renhua Wu, BGI-Shenzhen, China
Hui Jiang, BGI-Shenzhen, China
Xiao Liu, BGI-Shenzhen, China
Chang Yu, BGI-Shenzhen, China
Hancheng Zheng, BGI-Shenzhen, China
Min Jian, BGI-Shenzhen, China
Liping Nie, Peking University, China
Lei Wan, Department of Urology, Longgang Central Hospital, China
Min Shi, Peking University, China
Xiaojuan Sun, Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People’s Hospital, First Affiliated Hospital of Shenzhen University, China
Aifa Tang, Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People’s Hospital, First Affiliated Hospital of Shenzhen University, China
Guangwu Guo, BGI-Shenzhen, China
Yaoting Gui, Peking University, China
Zhiming Cai, Peking University, China
Jingxiang Li, BGI-Shenzhen, China
Wen Wang, CAS-Max Planck Junior Research Group, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences (CAS), China
Zuhong Lu, School of Biological Science and Medical Engineering, Southeast University, China
Background Cancers arise through an evolutionary process in which cell populations are subjected to selection; however, to date, the process of bladder cancer, which is one of the most common cancers in the world, remains unknown at a single-cell level.
Results We carried out single-cell exome sequencing of 66 individual tumor cells from a muscle-invasive bladder transitional cell carcinoma (TCC). Analyses of the somatic mutant allele frequency spectrum and clonal structure revealed that the tumor cells were derived from a single ancestral cell, but that subsequent evolution occurred, leading to two distinct tumor cell subpopulations. By analyzing recurrently mutant genes in an additional cohort of 99 TCC tumors, we identified genes that might play roles in the maintenance of the ancestral clone and in the muscle-invasive capability of subclones of this bladder cancer, respectively.
Conclusions This work provides a new approach of investigating the genetic details of bladder tumoral changes at the single-cell level and a new method for assessing bladder cancer evolution at a cell-population level.