Single-Cell Exome Sequencing Reveals Single-Nucleotide Mutation Characteristics of a Kidney Tumor

Xun Xu, Yong Hou, Xuyang Yin, Li Bao, Aifa Tang, Luting Song, Fuqiang Li, Shirley Tsang, Kui Wu, Hanjie Wu, Weiming He, Liang Zeng, Manjie Xing, Renhua Wu, Hui Jiang, Xiao Liu, Dandan Cao, Guangwu Guo, Xueda Hu, Yaoting Gui, Zesong Li, Wenyue Xie, Xiaojuan Sun, Min Shi, Zhiming Cai, Bin Wang, Meiming Zhong, Jingxiang Li, Zuhong Lu, Ning Gu, Xiuqing Zhang, Laurie Goodman, Lars Bolund, Jian Wang, Huanming Yang, Karsten Kristiansen, Michael Dean, Yingrui Li, Jun Wang

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.