A body map of somatic mutagenesis in morphologically normal human tissues (WGS)

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) of nine organs from five donors. We found that somatic mutation accumulations and clonal expansions are widespread, although to variable extents, 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 operate in multiple tissues from the same donor. We reconstructed the spatial somatic clonal architecture with sub-millimeter resolution. In esophagus and cardia, macroscopic somatic clones that expanded to hundreds of micrometers were frequently seen, whereas in tissues like colon, rectum, and duodenum, somatic clones were microscopic in size and evolved independently, possibly restricted by local tissue micro-structures. 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.EGA study EGAS00001005458