小柯机器人

吴晨、白凡、王建斌、黄岩谊和林东昕研究组合作绘制了正常人体组织中体细胞诱变的身体图谱。该项研究成果发表在2021年8月25日出版的《自然》上。

他们对来自 5 个供体的 9 个器官的 1,737 个形态正常组织活检进行了全面的基因组分析。他们发现体细胞突变积累和克隆扩增在形态正常的人体组织中很普遍，尽管程度不同。除了来自食道和贲门的组织外，很少检测到体细胞拷贝数改变。具有 SBS1 和 SBS5 突变特征的内源性突变过程在正常组织中普遍存在，尽管它们表现出不同的相对活性。

外源性突变过程在来自同一供体的多个组织中起作用。他们以亚毫米分辨率重建了空间体细胞克隆结构。在食道和贲门中，肉眼可见的体细胞克隆经常扩大到数百微米，而在结肠、直肠和十二指肠等组织中，体细胞克隆体微小且独立进化，可能受局部组织微观结构的限制。他们的研究描绘了来自同一个体的体细胞突变和克隆扩增的身体图谱。

据介绍，在正常组织中积累的体细胞突变与衰老和疾病有关。

附：英文原文

Title: A body map of somatic mutagenesis in morphologically normal human tissues

Author: Li, Ruoyan, Di, Lin, Li, Jie, Fan, Wenyi, Liu, Yachen, Guo, Wenjia, Liu, Weiling, Liu, Lu, Li, Qiong, Chen, Liping, Chen, Yamei, Miao, Chuanwang, Liu, Hongjin, Wang, Yuqian, Ma, Yuling, Xu, Deshu, Lin, Dongxin, Huang, Yanyi, Wang, Jianbin, Bai, Fan, Wu, Chen

Issue&Volume: 2021-08-25

Abstract: Somatic mutations that accumulate in normal tissues are associated with ageing and disease1,2. Here we performed a comprehensive genomic analysis of 1,737 morphologically normal tissue biopsies of 9 organs from 5 donors. We found that somatic mutation accumulations and clonal expansions were widespread, although to variable extents, in morphologically normal human tissues. Somatic copy number alterations were rarely detected, except for in tissues from the oesophagus and cardia. Endogenous mutational processes with the SBS1 and SBS5 mutational signatures are ubiquitous among normal tissues, although they exhibit different relative activities. Exogenous mutational processes operate in multiple tissues from the same donor. We reconstructed the spatial somatic clonal architecture with sub-millimetre resolution. In the oesophagus and cardia, macroscopic somatic clones that expanded to hundreds of micrometres were frequently seen, whereas in tissues such as the colon, rectum and duodenum, somatic clones were microscopic in size and evolved independently, possibly restricted by local tissue microstructures. Our study depicts a body map of somatic mutations and clonal expansions from the same individual. Laser-capture microdissection and mini-bulk exome sequencing are combined to analyse somatic mutations in morphologically normal tissues from nine organs from five donors, revealing variation in mutation burdens, mutational signatures and clonal expansions.

DOI: 10.1038/s41586-021-03836-1

Source: https://www.nature.com/articles/s41586-021-03836-1

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
官方网址：http://www.nature.com/
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