1 Department of Biomedicine - Department of Human Genetics, Department of Biomedicine, Health, Aarhus University2 BGI-Shenzhen3 Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People’s Hospital, First Affiliated Hospital of Shenzhen University4 BioMatrix5 Cancer and Inflammation Program, National Cancer Institute at Frederick6 Peking University Shenzhen Hospital7 Department of Urology, Longgang Central Hospital8 CAS-Max Planck Junior Research Group, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences (CAS)9 School of Biological Science and Medical Engineering, Southeast University10 Department of Biomedicine - Forskning og uddannelse, Øst, Department of Biomedicine, Health, Aarhus University11 The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen12 Department of Biomedicine - Forskning og uddannelse, Øst, Department of Biomedicine, Health, Aarhus University
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.
Gigascience, 2012, Vol 1, Issue 12, p. 1-14
Single-cell exome sequencing; Bladder cancer; Tumor evolution; Population genetics