The mutational landscape of human somatic and germline cells.

Autor: Moore L; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK.; Department of Pathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Cagan A; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK., Coorens THH; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK., Neville MDC; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK., Sanghvi R; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK., Sanders MA; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK.; Department of Hematology, Erasmus University Medical Center, Rotterdam, Netherlands., Oliver TRW; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK.; Department of Pathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Leongamornlert D; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK., Ellis P; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK.; Inivata, Cambridge, UK., Noorani A; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK., Mitchell TJ; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK.; Department of Surgery, University of Cambridge, Cambridge, UK., Butler TM; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK., Hooks Y; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK., Warren AY; Department of Pathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Jorgensen M; Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK., Dawson KJ; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK., Menzies A; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK., O'Neill L; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK., Latimer C; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK., Teng M; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK., van Boxtel R; Princess Máxima Center for Pediatric Oncology and Oncode Institute, Utrecht, Netherlands., Iacobuzio-Donahue CA; Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Martincorena I; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK., Heer R; Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.; Newcastle Urology, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK., Campbell PJ; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK., Fitzgerald RC; MRC Cancer Unit, University of Cambridge, Cambridge, UK., Stratton MR; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK. mrs@sanger.ac.uk., Rahbari R; Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute, Hinxton, UK. rr11@sanger.ac.uk.
Jazyk: angličtina
Zdroj: Nature [Nature] 2021 Sep; Vol. 597 (7876), pp. 381-386. Date of Electronic Publication: 2021 Aug 25.
DOI: 10.1038/s41586-021-03822-7
Abstrakt: 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.
(© 2021. Crown.)
Databáze: MEDLINE
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