ENDOMETRIAL CANCER: Normal endometrial glands frequently harbour pathogenic somatically-acquired mutations in cancer genes, suggesting that the processes leading to cancer are initiated early in life.

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May 4, 2020

SCIENTIFIC

ENDOMETRIAL CANCER

Normal endometrial glands frequently harbour pathogenic somatically-acquired mutations in cancer genes, suggesting that the processes leading to cancer are initiated early in life.

The mutational landscape of normal human endometrial epithelium

Luiza Moore et al Nature volume 580, pages640–646(2020)

Abstract

All normal somatic cells are thought to acquire mutations, but understanding of the rates, patterns, causes and consequences of somatic mutations in normal cells is limited. The uterine endometrium adopts multiple physiological states over a lifetime and is lined by a gland-forming epithelium1,2. Here, using whole-genome sequencing, we show that normal human endometrial glands are clonal cell populations with total mutation burdens that increase at about 29 base substitutions per year and that are many-fold lower than those of endometrial cancers. Normal endometrial glands frequently carry ‘driver’ mutations in cancer genes, the burden of which increases with age and decreases with parity. Cell clones with drivers often originate during the first decades of life and subsequently progressively colonize the epithelial lining of the endometrium. Our results show that mutational landscapes differ markedly between normal tissues—perhaps shaped by differences in their structure and physiology—and indicate that the procession of neoplastic change that leads to endometrial cancer is initiated early in life.