The mutational landscape of human somatic and germline cells

被引：176

作者：

Moore, Luiza ^{[1
,2
]}

Cagan, Alex ^{[1
,8
]}

Coorens, Tim H. H. ^{[1
]}

Neville, Matthew D. C. ^{[1
]}

Sanghvi, Rashesh ^{[1
]}

Sanders, Mathijs A. ^{[1
,3
]}

Oliver, Thomas R. W. ^{[1
,2
]}

Leongamornlert, Daniel ^{[1
]}

Ellis, Peter ^{[1
,12
]}

Noorani, Ayesha ^{[1
]}

Mitchell, Thomas J. ^{[1
,4
]}

Butler, Timothy M. ^{[1
]}

Hooks, Yvette ^{[1
]}

Warren, Anne Y. ^{[2
]}

Jorgensen, Mette ^{[5
]}

Dawson, Kevin J. ^{[1
]}

Menzies, Andrew ^{[1
]}

O'Neill, Laura ^{[1
]}

Latimer, Calli ^{[1
]}

Teng, Mabel ^{[1
]}

van Boxtel, Ruben ^{[6
]}

Iacobuzio-Donahue, Christine A. ^{[7
]}

Martincorena, Inigo ^{[1
]}

Heer, Rakesh ^{[9
,10
]}

Campbell, Peter J. ^{[1
]}

Fitzgerald, Rebecca C. ^{[11
]}

Stratton, Michael R. ^{[1
]}

Rahbari, Raheleh ^{[1
]}

机构：

[1] Wellcome Sanger Inst, Canc Ageing & Somat Mutat CASM, Hinxton, England

[2] Univ Cambridge, Dept Pathol, Hosp NHS Fdn Trust, Cambridge, England

[3] Erasmus Univ, Dept Hematol, Med Ctr, Rotterdam, Netherlands

[4] Univ Cambridge, Dept Surg, Cambridge, England

[5] Great Ormond St Hosp Children NHS Fdn Trust, London, England

[6] Princess Maxima Ctr Pediat Oncol & Oncode Inst, Utrecht, Netherlands

[7] Johns Hopkins Univ, Dept Pathol, Sol Goldman Pancreat Canc Res Ctr, Sch Med, Baltimore, MD USA

[8] Johns Hopkins Univ, Dept Oncol, Sidney Kimmel Comprehens Canc Ctr, Sch Med, Baltimore, MD USA

[9] Newcastle Univ, Translat & Clin Res Inst, Fac Med Sci, Newcastle Upon Tyne, England

[10] Newcastle Tyne Hosp NHS Fdn Trust, Freeman Hosp, Newcastle Urol, Newcastle Upon Tyne, England

[11] Univ Cambridge, MRC Canc Unit, Cambridge, England

[12] Inivata, Cambridge, England

来源：

NATURE | 2021年 / 597卷 / 7876期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

DE-NOVO MUTATIONS; EVOLUTION; SIGNATURES; SELECTION; CANCER; RATES; PATTERNS; AGE;

D O I：

10.1038/s41586-021-03822-7

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Over the course of an individual's lifetime, normal human cells accumulate mutations(1). Here we compare the mutational landscape in 29 cell types from the soma and germline using multiple samples from the same individuals. Two ubiquitous mutational signatures, SBS1 and SBS5/40, accounted for the majority of acquired mutations in most cell types, but their absolute and relative contributions varied substantially. SBS18, which potentially reflects oxidative damage(2), and several additional signatures attributed to exogenous and endogenous exposures contributed mutations to subsets of cell types. The rate of mutation was lowest in spermatogonia, the stem cells from which sperm are generated and from which most genetic variation in the human population is thought to originate. This was due to low rates of ubiquitous mutational processes and may be partially attributable to a low rate of cell division in basal spermatogonia. These results highlight similarities and differences in the maintenance of the germline and soma.

引用

页码：381 / +

页数：23

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[1] The mutational landscape of human somatic and germline cells
Luiza Moore
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