Institut for Biomedicin

Lars Bolund

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

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Dokumenter

DOI

  • Yingrui Li, BGI-Shenzhen, Kina
  • Xun Xu, BGI-Shenzhen, Kina
  • Luting Song, BGI-Shenzhen, Kina
  • Yong Hou, BGI-Shenzhen, Kina
  • Zesong Li, Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People’s Hospital, First Affiliated Hospital of Shenzhen University, Kina
  • Shirly Tsang, BioMatrix, USA
  • Fugiang Li, BGI-Shenzhen, Kina
  • Kate McGee, Cancer and Inflammation Program, National Cancer Institute at Frederick, USA
  • Kui Wu, BGI-Shenzhen, Kina
  • Hanjie Wu, BGI-Shenzhen, Kina
  • Xiaofei Ye, BGI-Shenzhen, Kina
  • Guibo Li, BGI-Shenzhen, Kina
  • Linlin Wang, BGI-Shenzhen, Kina
  • Bo Zhang, BGI-Shenzhen
  • ,
  • Jie Liang, BGI-Shenzhen, Kina
  • Wei Xie, BGI-Shenzhen, Kina
  • Renhua Wu, BGI-Shenzhen, Kina
  • Hui Jiang, BGI-Shenzhen, Kina
  • Xiao Liu, BGI-Shenzhen, Kina
  • Chang Yu, BGI-Shenzhen, Kina
  • Hancheng Zheng, BGI-Shenzhen, Kina
  • Min Jian, BGI-Shenzhen, Kina
  • Liping Nie, Peking University Shenzhen Hospital, Kina
  • Lei Wan, Department of Urology, Longgang Central Hospital, Kina
  • Min Shi, Peking University Shenzhen Hospital, Kina
  • Xiaojuan Sun, Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People’s Hospital, First Affiliated Hospital of Shenzhen University, Kina
  • Aifa Tang, Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People’s Hospital, First Affiliated Hospital of Shenzhen University, Kina
  • Guangwu Guo, BGI-Shenzhen, Kina
  • Yaoting Gui, Peking University Shenzhen Hospital, Kina
  • Zhiming Cai, Peking University Shenzhen Hospital, Kina
  • Jingxiang Li, BGI-Shenzhen, Kina
  • Wen Wang, CAS-Max Planck Junior Research Group, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences (CAS), Kina
  • Zuhong Lu, School of Biological Science and Medical Engineering, Southeast University, Kina
  • Xiuging Zhang, BGI-Shenzhen, Kina
  • Lars Bolund
  • Karsten Kristiansen, The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Danmark
  • Jian Wang, BGI-Shenzhen, Kina
  • Huanming Yang, BGI-Shenzhen, Kina
  • Michael Dean, Cancer and Inflammation Program, National Cancer Institute at Frederick, USA
  • Jun Wang, BGI-Shenzhen, Kina
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.
OriginalsprogEngelsk
TidsskriftGigaScience
Vol/bind1
Nummer12
Sider (fra-til)1-14
Antal sider14
ISSN2047-217X
DOI
StatusUdgivet - dec. 2012

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