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, Xiaoliang Sunney A1 - Zhang, Ning T1 - Single-cell sequencing deciphers a convergent evolution of copy number alterations from primary to circulating tumour cells Y1 - 2017/05/09 JF - Genome Research JO - Genome Research DO - 10.1101/gr.216788.116 SP - gr.216788.116 UR - http://genome.cshlp.org/content/early/2017/05/08/gr.216788.116.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 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. ER -