Punctuated copy number evolution and clonal stasis in triple-negative breast cancer

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Punctuated copy number evolution and clonal stasis in triple-negative breast cancer

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Title: Punctuated copy number evolution and clonal stasis in triple-negative breast cancer
Author: Gao, Ruli; Davis, Alexander; McDonald, Thomas; Sei, Emi; Shi, Xiuqing; Wang, Yong; Tsai, Pei-Ching; Casasent, Anna; Waters, Jill; Zhang, Hong; Meric-Bernstam, Funda; Michor, Franziska L.; Navin, Nicholas E.

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Citation: Gao, Ruli, Alexander Davis, Thomas O McDonald, Emi Sei, Xiuqing Shi, Yong Wang, Pei-Ching Tsai, et al. 2016. “Punctuated Copy Number Evolution and Clonal Stasis in Triple-Negative Breast Cancer.” Nature Genetics (August 15). doi:10.1038/ng.3641.
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Abstract: Aneuploidy is a hallmark of breast cancer; however, our knowledge of how these complex rearrangements evolve during tumorigenesis is limited. In this study we developed a highly-multiplexed single-nucleus-sequencing (HM-SNS) method to investigate DNA copy number evolution in triple-negative breast cancer (TNBC) patients. We applied this method to sequence 1000 single cells from 12 TNBC patients and identified 1-3 major clonal subpopulations in each tumor, with large genetic distances from the ancestral diploid cells. Mathematical modeling suggests that these data are unlikely to be explained by the gradual accumulation of copy number aberrations (CNAs) over extended periods of time. We also identified a minor (~7%) subpopulation of non-clonal cells that were classified as: 1) metastable tumor cells, 2) pseudo-diploid cells, and 3) chromazemic cells. Collectively, these data challenge the paradigm of gradual copy number evolution by showing that the majority of CNAs are acquired early in tumor evolution, in short punctuated bursts, followed by stable clonal expansions that form the tumor mass. These data have important implications for understanding the evolutionary dynamics of tumor growth and the diagnosis and treatment of TNBC patients.
Published Version: 10.1038/ng.3641
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:28557197
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