1 Department of Biology, Faculty of Science, Københavns Universitet2 Section for Metabolic Genetics, Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, Københavns Universitet3 unknown4 Institut for Biomedicin - Human Genetik5 Genome Research and Molecular Bio Medicine, Department of Biology, Faculty of Science, Københavns Universitet6 Department of Biology, Faculty of Science, Københavns Universitet7 Genome Research and Molecular Bio Medicine, Department of Biology, Faculty of Science, Københavns Universitet8 Department of Biology, Faculty of Science, Københavns Universitet
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