| 描述信息 |
Somatic mutations accumulated in normal tissues are associated with aging and disease. Here we performed a comprehensive genomic analysis of 1,736 biopsy samples collected from morphologically normal tissues of nine organs from five donors. Through in-depth within and between individual comparison, we found that somatic mutations and clonal expansion are widespread in normal (epithelial) tissues, and the degree of clonal expansion and enrichment of driver mutations display strong organ dependence. Interestingly, somatic copy number alterations were frequently detected in normal tissues from esophagus and cardia. Mutational signature analysis further delineated the endogenous and exogeneous factors that contribute to somatic mutations in different human organs. By building a 3D phylogeny map based on mutations detected in biopsy samples, we reconstructed the somatic clonal architecture in normal tissues. In tissues from esophagus, cardia, and liver, macroscopic somatic clones expanded to ~1 mm were commonly seen, whereas in tissues from colon, rectum, and ???, somatic clones were microscopic in size and evolved independently. Our study depicts a body map of somatic mutation and clonal expansion from the same individual, and reveals organ-specific features which could be shaped by variations in tissue turnover rates and physiological microenvironment of different organs. |
