Single-cell sequencing analysis characterizes common and cell-lineage-specific mutations in a muscle-invasive bladder cancer

Research output: Contribution to journalJournal articleResearchpeer-review

  • Yingrui Li
  • Xun Xu
  • Luting Song
  • Yong Hou
  • Zesong Li
  • Shirley Tsang
  • Fuqiang Li
  • Kate Im
  • Kui Wu
  • Hanjie Wu
  • Xiaofei Ye
  • Guibo Li
  • Linlin Wang
  • Bo Zhang
  • Jie Liang
  • Wei Xie
  • Renhua Wu
  • Hui Jiang
  • Xiao Liu
  • Chang Yu
  • Hancheng Zheng
  • Min Jian
  • Liping Nie
  • Lei Wan
  • Min Shi
  • Xiaojuan Sun
  • Aifa Tang
  • Guangwu Guo
  • Yaoting Gui
  • Zhiming Cai
  • Jingxiang Li
  • Wen Wang
  • Zuhong Lu
  • Xiuqing Zhang
  • Lars Bolund
  • Jian Wang
  • Huanming Yang
  • Michael Dean
  • Jun Wang
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.
Original languageEnglish
Issue number12
Number of pages14
Publication statusPublished - 2012

ID: 40906148