TY - JOUR 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 Y1 - 2017/08/01 JF - Genome Research JO - Genome Research SP - 1312 EP - 1322 DO - 10.1101/gr.216788.116 VL - 27 IS - 8 UR - http://genome.cshlp.org/content/27/8/1312.abstract N2 - 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. ER -