生物
癌症的体细胞进化
食管
体细胞
种系突变
突变
遗传学
基因
解剖
作者
Ruoyan Li,Lin Di,Jie Li,Wenyi Fan,Yachen Liu,Wenjia Guo,Weiling Liu,Lu Liu,Qiong Li,Liping Chen,Yamei Chen,Chuanwang Miao,Hongjin Liu,Yuqian Wang,Yuling Ma,Deshu Xu,Dongxin Lin,Yanyi Huang,Jianbin Wang,Fan Bai
标识
DOI:10.1101/2020.11.30.403436
摘要
Abstract Somatic mutations accumulated in normal tissues are associated with aging and disease. Here, we performed a comprehensive genomic analysis of 1,737 morphologically normal tissue biopsies (~ 600 cells each), mostly from the epithelia, of nine organs from five donors. We found that somatic mutation accumulations and clonal expansions are widespread, although with variable extent, in morphologically normal human tissues. Somatic copy number alterations were rarely detected, except for tissues from esophagus and cardia. Endogenous mutational processes like SBS1 and SBS5 are ubiquitous among normal tissues though exhibiting different relative activities. Exogenous mutational processes like SBS22 were found in different tissues from the same donor. We reconstructed the spatial somatic clonal architecture with sub-millimeter resolution. In epithelial tissues from esophagus and cardia, macroscopic somatic clones expanded to several millimeters were frequently seen, whereas in tissues from colon, rectum, and duodenum somatic clones were microscopic in size and evolved independently. Our study depicted a body map of somatic mutations and clonal expansions from the same individuals, and it revealed that the degree of somatic clonal expansion and enrichment of driver mutations are highly organ specific.
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