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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 paper provides the first survey of clock-like mutational processes operating in human somatic cells.

Authors:
ORCiD logo [1];  [2];  [3];  [4];  [2];  [5];  [3]
  1. Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Wellcome Trust Sanger Institute, Hinxton (United Kingdom)
  2. Wellcome Trust Sanger Institute, Hinxton (United Kingdom); Univ. of Cambridge, Cambridge (United Kingdom)
  3. Wellcome Trust Sanger Institute, Hinxton (United Kingdom)
  4. MRC Lab. of Molecular Biology, Cambridge (United Kingdom)
  5. Wellcome Trust Sanger Institute, Hinxton (United Kingdom); Addenbrooke's Hospital National Health Service (NHS) Trust, Cambridge (United Kingdom)
Publication Date:
Research Org.:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1236704
Report Number(s):
LA-UR-15-21254
Journal ID: ISSN 1061-4036; ng.3441
Grant/Contract Number:  
AC52-06NA25396
Resource Type:
Accepted Manuscript
Journal Name:
Nature Genetics
Additional Journal Information:
Journal Volume: 47; Journal Issue: 12; Journal ID: ISSN 1061-4036
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; cancer; computational biology and bioinformatics; genomics

Citation Formats

Alexandrov, Ludmil B., Jones, Philip H., Wedge, David C., Sale, Julian E., Campbell, Peter J., Nik-Zainal, Serena, and Stratton, Michael R. Clock-like mutational processes in human somatic cells. United States: N. p., 2015. Web. doi:10.1038/ng.3441.
Alexandrov, Ludmil B., Jones, Philip H., Wedge, David C., Sale, Julian E., Campbell, Peter J., Nik-Zainal, Serena, & Stratton, Michael R. Clock-like mutational processes in human somatic cells. United States. doi:10.1038/ng.3441.
Alexandrov, Ludmil B., Jones, Philip H., Wedge, David C., Sale, Julian E., Campbell, Peter J., Nik-Zainal, Serena, and Stratton, Michael R. Mon . "Clock-like mutational processes in human somatic cells". United States. doi:10.1038/ng.3441. https://www.osti.gov/servlets/purl/1236704.
@article{osti_1236704,
title = {Clock-like mutational processes in human somatic cells},
author = {Alexandrov, Ludmil B. and Jones, Philip H. and Wedge, David C. and Sale, Julian E. and Campbell, Peter J. and Nik-Zainal, Serena and Stratton, Michael R.},
abstractNote = {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 paper provides the first survey of clock-like mutational processes operating in human somatic cells.},
doi = {10.1038/ng.3441},
journal = {Nature Genetics},
number = 12,
volume = 47,
place = {United States},
year = {2015},
month = {11}
}

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