Single-cell sequencing deciphers a convergent evolution of copy number alterations from primary to circulating tumour cells
- Yan Gao1,
- Xiaohui Ni2,
- Hua Guo3,
- Zhe Su1,
- Yi Ba3,
- Zhongsheng Tong3,
- Zhi Guo3,
- Xin Yao3,
- Xixi Chen1,
- Jian Yin3,
- Zhao Yan3,
- Lin Guo3,
- Ying Liu1,
- Fan Bai1,
- Xiaoliang Sunney Xie2 and
- Ning Zhang3,4
- 1 Peking University;
- 2 Harvard University;
- 3 Tianjin Medical University Cancer Institute and Hospital
- ↵* Corresponding author; email: zhangning{at}tmu.edu.cn
Abstract
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.
- Received October 4, 2016.
- Accepted May 3, 2017.
- Published by Cold Spring Harbor Laboratory Press
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