[Somatic Mosaicism and Clonal Evolution]

Cancer originates from a single ancestor cell that acquires driver mutations, which confer a selective growth advantage, followed by the acquisition of additional driver mutations by descendant cells. Recently, it has become evident that somatic mutations accumulate even in normal cells with aging; exposure to environmental factors such as alcohol, smoking, and ultraviolet radiation increases this mutation rate. Clones harboring cancer driver mutations expand even in normal tissues with age, leading to tissue remodeling known as somatic mosaicism. Chronic inflammatory diseases can also influence this remodeling, and identification of disease-specific driver mutations can help elucidate the pathogenesis of such diseases. Phylogenetic analysis of cancer and surrounding tissues, including normal cells, has revealed the early evolutionary history of carcinogenesis. In addition, accumulating evidence that somatic mosaicism in the blood affects various diseases-including atherosclerosis and chronic liver disease-highlights the potential role of somatic mosaicism in non-neoplastic disease pathogenesis. This article summarizes recent updates on somatic mosaicism in normal tissues.