生物
循环肿瘤细胞
转移
原发性肿瘤
癌症研究
PTEN公司
基因复制
拷贝数变化
肿瘤进展
基因
癌症
染色体不稳定性
基因组不稳定性
染色体
遗传学
基因组
DNA
PI3K/AKT/mTOR通路
DNA损伤
信号转导
作者
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
出处
期刊:Genome Research
[Cold Spring Harbor Laboratory]
日期:2017-05-09
卷期号:27 (8): 1312-1322
被引量:68
标识
DOI:10.1101/gr.216788.116
摘要
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.
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