Genomic Analyses of Circulating Tumor Cells
Originating from primary tumors, circulating tumor cells (CTCs) enter peripheral blood and seed metastases, which account for the majority of cancer-related deaths. The genome sequencing of CTCs could offer non-invasive prognosis or even diagnosis, but has been hampered by low single cell genome coverage of scarce CTCs.
In collaboration with colleagues at Cancer Hospital and BIOPIC of Peking University, we applied MALBAC for whole genome amplification of single CTCs from lung cancer patients. We observed characteristic cancer-associated single nucleotide variations and insertions/deletions in exomes of CTCs. These mutations provided information needed for individualized therapy, such as drug resistance and phenotypic transition, but were heterogeneous from cell to cell.
We discovered that, unlike the highly heterogeneous point mutations, copy number variation (CNV) patterns of the circulating tumor cells are reproducible within a patient, and even within different patients of the same cancer type, but are distinctly different for different cancer types. This offers a potential cancer diagnosis based on the CNV patterns. This result also raised intriguing questions on the genesis of metastasis, which can be studied further by our single cell genomics experiments.
Ni, Xiaohui; Zhuo, Minglei; Su, Zhe; Duan, Jianchun; Gao, Yan; Wang, Zhijie; Zong, Chenghang; Bai, Hua; Chapman, Alec R.; Zhao, Jun; Xu, Liya; An, Tongtong; Ma, Qi; Wang, Yuyan; Wu, Meina; Sun, Yu; Wang, Shuhang; Li, Zhenxiang; Yang, Xiaodan; Yong, Jun; Su, Xiao-Dong; Lu, Youyong; Bai, Fan; Xie, X. Sunney; Wang, Jie. “Reproducible copy number variation patterns among single circulating tumor cells of lung cancer patients,” PNAS 110, 21083-21088 DOI: 10.1073/pnas.1320659110 (2013)