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, X. Sunney
A1 Zhang, Ning
T1 Single-cell sequencing deciphers a convergent evolution of copy number alterations from primary to circulating tumor cells
JF Genome Research 
JO Genome Research 
YR 2017 
FD August 01 
VO 27 
IS 8 
SP 1312 
OP 1322 
DO 10.1101/gr.216788.116 
UL http://genome.cshlp.org/content/27/8/1312.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 tumor cells and circulating tumor cells (CTCs) from the same patient. Single-nucleotide variants (SNVs) in single cells from both samples occurred sporadically, whereas CNAs among primary tumor cells emerged accumulatively rather than abruptly, converging toward the CNA in CTCs. Focal CNAs affecting the MYC gene and the PTEN gene were observed only in a minor portion of primary tumor cells but were present in all CTCs, suggesting a strong selection toward metastasis. Single-cell structural variant (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.