Although it is assumed that all normal somatic cells acquire mutations, knowledge of the rates, patterns, causes, and implications of somatic mutations in normal cells is limited. Over the course of a woman’s life, the uterine endometrium changes physiological states and is lined by a gland-forming epithelium. 

Researchers show that normal human endometrial glands are clonal cell populations with overall mutation loads that rise at roughly 29 base substitutions per year and are many-fold lower than those of endometrial malignancies using whole-genome sequencing. Normal endometrial glands commonly have ‘driver’ mutations in cancer genes, the prevalence of which rises with age and falls with parity. Cell clones with drivers are frequently formed throughout the early decades of life and then invade the endometrial epithelial lining gradually. 


The findings suggest that the mutational landscapes of normal tissues differ significantly, possibly due to changes in structure and function, and that the process of neoplastic transformation that leads to endometrial cancer begins early in life.