期刊
NATURE
卷 597, 期 7876, 页码 398-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41586-021-03836-1
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资金
- National Natural Science Foundation of China [81725015, 81988101, 22050004, 22050002]
- Beijing Outstanding Young Scientist Program [BJJWZYJH01201910023027]
- Medical and Health Technology Innovation Project of the Chinese Academy of Medical Sciences [2019-I2M-2-001]
- National Key R&D Program of China [2019YFC1315702, 2018ZX10302205, 2018YFA0108100]
- Guangdong Province Key Research and Development Program [2019B020226002]
- Beijing Municipal Science and Technology Commission [Z201100005320016]
- Beijing Advanced Innovation Center for Genomics
- Shenzhen Bay Laboratory
Somatic mutations and clonal expansions in normal tissues are widespread but vary in extent and activity. External and endogenous mutational processes both play a role.
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.
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