title: Clock-like mutational processes in human somatic cells.
abstract: During the course of a lifetime, somatic cells acquire mutations. Different mutational processes may contribute to the mutations accumulated in a cell, with each imprinting a mutational signature on the cell's genome. Some processes generate mutations throughout life at a constant rate in all individuals, and the number of mutations in a cell attributable to these processes will be proportional to the chronological age of the person. Using mutations from 10,250 cancer genomes across 36 cancer types, we investigated clock-like mutational processes that have been operating in normal human cells. Two mutational signatures show clock-like properties. Both exhibit different mutation rates in different tissues. However, their mutation rates are not correlated, indicating that the underlying processes are subject to different biological influences. For one signature, the rate of cell division may influence its mutation rate. This study provides the first survey of clock-like mutational processes operating in human somatic cells.
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.|Theoretical Biology and Biophysics (T-6), Los Alamos National Laboratory, Los Alamos, New Mexico, USA.|Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, New Mexico, USA.
authors.forename: Ludmil B
authors.identifier: http://orcid.org/0000-0003-3596-4515
authors.initials: LB
authors.lastname: Alexandrov
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.|Medical Research Council (MRC) Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, UK.
authors.forename: Philip H
authors.initials: PH
authors.lastname: Jones
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: David C
authors.initials: DC
authors.lastname: Wedge
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: Julian E
authors.initials: JE
authors.lastname: Sale
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.|Department of Haematology, University of Cambridge, Cambridge, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Campbell
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.|Department of Medical Genetics, Addenbrooke's Hospital National Health Service (NHS) Trust, Cambridge, UK.
authors.forename: Serena
authors.initials: S
authors.lastname: Nik-Zainal
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Stratton
mesh_terms: D001683:Biological Clocks / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004622:Embryo, Mammalian / Q000166:cytology* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006801:Humans; D009154:Mutation / Q000235:genetics*; D059645:Mutation Rate; D009369:Neoplasms / Q000145:classification / Q000235:genetics*