Single-cell Sequencing Deciphers a Convergent Evolution of Copy Number Alterations from Primary to Circulating Tumor Cells

Overview

Journal Genome Res

Specialty Genetics

Date 2017 May 11

PMID 28487279

Citations 55

Authors

Yan Gao

Xiaohui Ni

Hua Guo

Zhe Su

Yi Ba

Zhongsheng Tong

Zhi Guo

Xin Yao

Xixi Chen

Jian Yin

Zhao Yan

Lin Guo

Ying Liu

Fan Bai

X Sunney Xie

Ning Zhang

Affiliations

Soon will be listed here.

Abstract

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 gene and the 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.

Citing Articles

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