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

GigaScience

Jun Wang⁷  Michael Dean^1,10  Huanming Yang^1,11  Jian Wang^1,11  Karsten Kristiansen²  Lars Bolund^1,12  Xiuqing Zhang^1,11  Zuhong Lu⁹  Wen Wang⁶  Jingxiang Li^1,11  Zhiming Cai⁵  Yaoting Gui⁵  Guangwu Guo^1,11  Aifa Tang⁸  Xiaojuan Sun⁸  Min Shi⁵  Lei Wan³  Liping Nie⁵  Min Jian^1,11  Hancheng Zheng^1,11  Chang Yu^1,11  Xiao Liu^1,11  Hui Jiang^1,11  Renhua Wu^1,11  Wei Xie⁹  Jie Liang^1,11  Bo Zhang^1,11  Linlin Wang^1,11  Guibo Li^1,11  Xiaofei Ye^1,11  Hanjie Wu¹  Kui Wu^1,11  Kate McGee Im^1,10  Fuqiang Li^1,11  Shirley Tsang⁴  Zesong Li⁸  Yong Hou⁹  Luting Song^1,13  Xun Xu^1,11  Yingrui Li^1,11 

[1] School of Bioscience and Biotechnology, Guangzhou Higher Education Mega Centre, South China University of Technology, Panyu District, Guangzhou, 510006, People’s Republic of China;The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Ole Maaløes Vej 5, Copenhagen, DK, 2200, Denmark;Department of Urology, Longgang Central Hospital, Shenhui Road, Longgang Town, Shenzhen, 518116, People’s Republic of China;BioMatrix, LLC, 3029 Windy Knoll Court, Rockville, MD, 20850, USA;Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Shenzhen PKU-HKUST Medical Center, Peking University Shenzhen Hospital, 1120 Lian Hua Road, Futian District, Shenzhen, 518036, People’s Republic of China;CAS-Max Planck Junior Research Group, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences (CAS), 32# Jiao-chang Road, Kunming, Yunnan, 650223, People’s Republic of China;Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, Copenhagen, DK, 2200, Denmark;The Institute of Urogenital Diseases, Shenzhen University, Shenzhen, 518060, People’s Republic of China;State Key Laboratory of Bioelectronics, Southeast University, Sipailou 2#, Nanjing, 210096, People’s Republic of China;Cancer and Inflammation Program, National Cancer Institute at Frederick, Building 560, Frederick, MD, 21702, USA;BGI-Shenzhen, Beishan Industrial Zone, Beishan Road, Yantian, Shenzhen, 518083, People’s Republic of China;Institute of Human Genetics, University of Aarhus, Aarhus, 8100, Denmark;College of Life Sciences, Wuhan University, Luojia Hill, Wuhan, 430072, People’s Republic of China

关键词: Population genetics;    Tumor evolution;    Bladder cancer;    Single-cell exome sequencing;   

Others  :  861886
DOI  :  10.1186/2047-217X-1-12

 received in 2012-04-09, accepted in 2012-08-02,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Li et al.; licensee BioMed Central Ltd.

【 图 表 】

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