Tobacco smoking and somatic mutations in human bronchial epithelium

doi:10.1038/s41586-020-1961-1

GSTDTAP > 地球科学

DOI	10.1038/s41586-020-1961-1
	Tobacco smoking and somatic mutations in human bronchial epithelium
	Sharma, Nikhil 1,2; Flaherty, Kali 1,2; Lezgiyeva, Karina 1,2; Wagner, Daniel E.3; Klein, Allon M.3; Ginty, David D.1,2
	2020-01-16
发表期刊	NATURE
ISSN	0028-0836
EISSN	1476-4687
出版年	2020
卷号	578 期号:7794 页码:266-+
文章类型	Article
语种	英语
国家	England; Japan
英文关键词	Whole-genome sequencing of normal bronchial epithelium from 16 individuals shows that tobacco smoking increases genomic heterogeneity, mutational burden and driver mutations, whereas stopping smoking promotes replenishment of the epithelium with near-normal cells. Tobacco smoking causes lung cancer(1-3), a process that is driven by more than 60 carcinogens in cigarette smoke that directly damage and mutate DNA(4,5). The profound effects of tobacco on the genome of lung cancer cells are well-documented(6-10), but equivalent data for normal bronchial cells are lacking. Here we sequenced whole genomes of 632 colonies derived from single bronchial epithelial cells across 16 subjects. Tobacco smoking was the major influence on mutational burden, typically adding from 1,000 to 10,000 mutations per cell massively increasing the variance both within and between subjects and generating several distinct mutational signatures of substitutions and of insertions and deletions. A population of cells in individuals with a history of smoking had mutational burdens that were equivalent to those expected for people who had never smoked: these cells had less damage from tobacco-specific mutational processes, were fourfold more frequent in ex-smokers than current smokers and had considerably longer telomeres than their more-mutated counterparts. Driver mutations increased in frequency with age, affecting 4-14% of cells in middle-aged subjects who had never smoked. In current smokers, at least 25% of cells carried driver mutations and 0-6% of cells had two or even three drivers. Thus, tobacco smoking increases mutational burden, cell-to-cell heterogeneity and driver mutations, but quitting promotes replenishment of the bronchial epithelium from mitotically quiescent cells that have avoided tobacco mutagenesis.
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:000513110500026
WOS关键词	LUNG-CANCER ; DNA-DAMAGE ; SIGNATURES ; GENOME ; EVOLUTION ; EXPANSION ; SELECTION ; PATTERNS ; CELLS
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/281235
专题	地球科学资源环境科学气候变化
作者单位	1.Harvard Med Sch, Dept Neurobiol, Boston, MA 02115 USA; 2.Harvard Med Sch, Howard Hughes Med Inst, Boston, MA 02115 USA; 3.Harvard Med Sch, Dept Syst Biol, Boston, MA 02115 USA
推荐引用方式 GB/T 7714	Sharma, Nikhil,Flaherty, Kali,Lezgiyeva, Karina,et al. Tobacco smoking and somatic mutations in human bronchial epithelium[J]. NATURE,2020,578(7794):266-+.
APA	Sharma, Nikhil,Flaherty, Kali,Lezgiyeva, Karina,Wagner, Daniel E.,Klein, Allon M.,&Ginty, David D..(2020).Tobacco smoking and somatic mutations in human bronchial epithelium.NATURE,578(7794),266-+.
MLA	Sharma, Nikhil,et al."Tobacco smoking and somatic mutations in human bronchial epithelium".NATURE 578.7794(2020):266-+.