Single-cell Exome Sequencing and Novel Mutation Characteristics of Kidney Cancer

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 indicated this tumor was unlikely to have resulted from mutations in VHL and PBRM1. Quantitative population genetic analysis indicated 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 delineate a detailed intratumoral genetic landscape at a single-cell level. Our pilot study demonstrates ccRCC may be more genetically complex than previously thought and provides novel information that can lead to new ways to investigate individual tumors with the aim of developing more effective cellular targeted therapies.