The mutational landscape of normal human endometrial epithelium

doi:10.1038/s41586-020-2214-z

GSTDTAP > 地球科学

DOI	10.1038/s41586-020-2214-z
	The mutational landscape of normal human endometrial epithelium
	Rogelj, Joeri; Forster, Piers M.; Kriegler, Elmar; Smith, Christopher J.; Seferian, Roland
	2020-03-25
发表期刊	NATURE
ISSN	0028-0836
EISSN	1476-4687
出版年	2020
卷号	580 期号:7805 页码:640-+
文章类型	Article
语种	英语
国家	England; Netherlands; USA
英文关键词	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 epithelium(1,2). 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. Whole-genome sequencing of normal human endometrial glands shows that most are clonal cell populations and frequently carry cancer driver mutations that occur early in life, and that parity has a protective effect.
领域	地球科学 ; 气候变化 ; 资源环境
收录类别	SCI-E
WOS记录号	WOS:000528166900001
WOS关键词	CANCER-ASSOCIATED MUTATIONS ; SOMATIC MUTATIONS ; STEM-CELLS ; CLONAL HEMATOPOIESIS ; RISK ; DIVERSIFICATION ; EXPANSION ; SELECTION ; PATTERN
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/281445
专题	地球科学资源环境科学气候变化
推荐引用方式 GB/T 7714	Rogelj, Joeri,Forster, Piers M.,Kriegler, Elmar,et al. The mutational landscape of normal human endometrial epithelium[J]. NATURE,2020,580(7805):640-+.
APA	Rogelj, Joeri,Forster, Piers M.,Kriegler, Elmar,Smith, Christopher J.,&Seferian, Roland.(2020).The mutational landscape of normal human endometrial epithelium.NATURE,580(7805),640-+.
MLA	Rogelj, Joeri,et al."The mutational landscape of normal human endometrial epithelium".NATURE 580.7805(2020):640-+.