RT Journal
A1 Gao, Yan
A1 Ni, Xiaohui
A1 Guo, Hua
A1 Su, Zhe
A1 Ba, Yi
A1 Tong, Zhongsheng
A1 Guo, Zhi
A1 Yao, Xin
A1 Chen, Xixi
A1 Yin, Jian
A1 Yan, Zhao
A1 Guo, Lin
A1 Liu, Ying
A1 Bai, Fan
A1 Xie, Xiaoliang Sunney
A1 Zhang, Ning
T1 Single-cell sequencing deciphers a convergent evolution of copy number alterations from primary to circulating tumour cells
JF Genome Research 
JO Genome Research 
YR 2017 
FD May 09 
DO 10.1101/gr.216788.116 
SP gr.216788.116 
UL http://genome.cshlp.org/content/early/2017/05/08/gr.216788.116.abstract 
AB Copy number alteration (CNA) is a major contributor to genome instability, a hallmark of cancer. Here we studied genomic alterations in single primary tumour cells and circulating tumour cells (CTCs) from the same patient. Single-nucleotide variations (SNVs) in single cells from both samples occurred sporadically, whereas CNAs among primary tumour cells emerged accumulatively rather than abruptly, converging toward that of CTCs. Focal CNAs affecting MYC gene and PTEN gene were observed only in a minor portion of primary tumour cells but were present in all CTCs, suggesting a strong selection toward metastasis. Single-cell structural variation (SV) analyses revealed a two-step mechanism, a complex rearrangement followed by gene amplification, for the simultaneous formation of anomalous CNAs in multiple chromosome regions. Integrative CNA analyses of 97 CTCs from 23 patients confirmed the convergence of CNAs and revealed single, concurrent, and mutually exclusive CNAs that could be the driving events in cancer metastasis.