생화학분자생물학회

	Kenichi Yoshida (keyoshi2@ncc.go.jp)
	2022-present	Chief, Division of Cancer Evolution, National Cancer Center Research Institute
	2020-2022	Postdoctoral fellow, Wellcome Sanger Institute
	2018-2020	Overseas Research Fellowship, Japan Society for the Promotion of Science
	2014-2018	Assistant Professor, Graduate School of Medicine, Kyoto University
	2010-2014	PhD program, The University of Tokyo
	2005-2007	Junior/Senior Resident, St. Luke’s International Hospital
	1999-2005	Undergraduate/MD program, School of Medicine, Tohoku University

Somatic mutations and clonal evolution in normal tissues and cancer development

Understanding the early stages of carcinogenesis requires detailed insight into the abnormalities present in normal cells before cancer onset. In the past, it was difficult to analyze genomic abnormalities in small clones in normal tissues. However, recent technological advances in genomic analysis have shed light on the process of accumulation of somatic mutations in normal cells, which is driven by factors such as aging and environmental influences. Even in normal tissues, clones that have acquired driver mutations-either directly contributing to carcinogenesis or adapting to specific pathological or genetic backgrounds-are frequently selected, leading to clonal expansion. Normal cells undergo clonal evolution into cancer cells over several decades, with the initial acquisition of a driver mutation occurring in early life. Here this review presents recent findings concerning the accumulation of somatic mutations in normal cells, acquisition of driver mutations and clonal evolution toward cancer.

Exp Mol Med. 2026 Apr;58(4):961-969. doi: 10.1038/s12276-025-01592-0
https://pubmed.ncbi.nlm.nih.gov/41331092/