A body map of somatic mutagenesis in morphologically normal human tissues
A body map of somatic mutagenesis in morphologically normal human tissues
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DOI：
10.1038/s41586-021-03836-1
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发表时间：
2021-08-25
期刊：
影响因子：
64.8
通讯作者：
Wu, Chen
中科院分区：
文献类型：
--
作者：
Li, Ruoyan;Di, Lin;Wu, Chen
在正常组织中积累的体细胞突变与衰老和疾病有关（1，2）。在这里，我们对来自5名供体的9个器官的1，737个形态正常的组织活检进行了全面的基因组分析。我们发现，体细胞突变积累和克隆扩张是广泛的，虽然在不同程度上，在形态正常的人体组织。体细胞拷贝数的改变很少被检测到，除了在食管和贲门的组织。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。我们重建的空间体细胞克隆结构与亚毫米分辨率。在食道和贲门，经常看到扩展到数百微米的宏观体细胞克隆，而在结肠，直肠和十二指肠等组织中，体细胞克隆的尺寸很小，并且独立进化，可能受到局部组织微观结构的限制。我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。
Somatic mutations that accumulate in normal tissues are associated with ageing and disease(1,2). 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.