Author:
Moore Luiza,Leongamornlert Daniel,Coorens Tim HH,Sanders Mathijs A,Ellis Peter,Dawson Kevin,Maura Franscesco,Nangalia Jyoti,Tarpey Patrick S,Brunner Simon F,Lee-Six Henry,Rahbari Raheleh,Moody Sarah,Hooks Yvette,Mahbubani Krishnaa,Jimenez-Linan Mercedes,Brosens Jan J,Iacobuzio-Donahue Christine,Martincorena Inigo,Saeb-Parsy Kourosh,Campbell Peter J,Stratton Michael R.
Abstract
All normal somatic cells are thought to acquire mutations. However, characterisation of the patterns and consequences of somatic mutation in normal tissues is limited. Uterine endometrium is a dynamic tissue that undergoes cyclical shedding and reconstitution and is lined by a gland-forming epithelium. Whole genome sequencing of normal endometrial glands showed that most are clonal cell populations derived from a recent common ancestor with mutation burdens differing from other normal cell types and manyfold lower than endometrial cancers. Mutational signatures found ubiquitously account for most mutations. Many, in some women potentially all, endometrial glands are colonised by cell clones carrying driver mutations in cancer genes, often with multiple drivers. Total and driver mutation burdens increase with age but are also influenced by other factors including body mass index and parity. Clones with drivers often originate during early decades of life. The somatic mutational landscapes of normal cells differ between cell types and are revealing the procession of neoplastic change leading to cancer.
Publisher
Cold Spring Harbor Laboratory
Cited by
11 articles.
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