小柯机器人

美国德克萨斯大学安德森癌症中心Nicholas E. Navin、哈佛大学Franziska Michor等研究人员合作发现，乳腺肿瘤在扩张过程中可维持亚克隆多样性。该项研究成果于2021年3月24日在线发表在《自然》杂志上。

研究人员表示，人们对原发性乳腺肿瘤扩展过程中拷贝数演变的了解是有限的。

为了调查这一过程，研究人员开发了一种单细胞、单分子DNA测序方法，并对来自8种人类三阴性乳腺癌和4种细胞系的16,178种单细胞进行了拷贝数分析。结果表明，乳腺肿瘤和细胞系包含很大的亚克隆环境，这些亚克隆组织为几个（3–5）主要的超级克隆。

进化分析表明，在克隆性TP53突变、多重杂合性丧失事件和基因组倍增之后，存在一段短暂的基因组不稳定性，随后在原发性肿瘤扩展期间出现了拷贝数进化。通过亚克隆培养中的单个子细胞，研究人员表明肿瘤细胞使它们的基因组多样化，并且不保留等基因特性。

这些数据表明，三阴性乳腺癌继续发展染色体畸变，并在原发性肿瘤生长过程中保持亚克隆多样性的储备。 

附：英文原文

Title: Breast tumours maintain a reservoir of subclonal diversity during expansion

Author: Darlan C. Minussi, Michael D. Nicholson, Hanghui Ye, Alexander Davis, Kaile Wang, Toby Baker, Maxime Tarabichi, Emi Sei, Haowei Du, Mashiat Rabbani, Cheng Peng, Min Hu, Shanshan Bai, Yu-wei Lin, Aislyn Schalck, Asha Multani, Jin Ma, Thomas O. McDonald, Anna Casasent, Angelica Barrera, Hui Chen, Bora Lim, Banu Arun, Funda Meric-Bernstam, Peter Van Loo, Franziska Michor, Nicholas E. Navin

Issue&Volume: 2021-03-24

Abstract: Our knowledge of copy number evolution during the expansion of primary breast tumours is limited1,2. Here, to investigate this process, we developed a single-cell, single-molecule DNA-sequencing method and performed copy number analysis of 16,178 single cells from 8 human triple-negative breast cancers and 4 cell lines. The results show that breast tumours and cell lines comprise a large milieu of subclones (7–22) that are organized into a few (3–5) major superclones. Evolutionary analysis suggests that after clonal TP53 mutations, multiple loss-of-heterozygosity events and genome doubling, there was a period of transient genomic instability followed by ongoing copy number evolution during the primary tumour expansion. By subcloning single daughter cells in culture, we show that tumour cells rediversify their genomes and do not retain isogenic properties. These data show that triple-negative breast cancers continue to evolve chromosome aberrations and maintain a reservoir of subclonal diversity during primary tumour growth.

DOI: 10.1038/s41586-021-03357-x

Source: https://www.nature.com/articles/s41586-021-03357-x

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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