2025 Volume 101 Issue 7 Pages 394-413
The term “clone” is commonly used in the medical and life sciences to denote a genetically identical population, at both the individual and cellular levels. The concept of clonal expansion is of fundamental importance in cancer research. The advent of advanced sequencing technologies has elucidated the clonal nature of intermediates between normal cells and cancer cells. This review underscores seminal discoveries in the blood and stratified squamous epithelial systems, emphasizing the pivotal role of mutations in DNA modifier genes and Notch pathway genes, respectively, as drivers of clonal expansion. Despite the distinct nature of these systems and their genetic backgrounds, a common biological principle emerges.