Cited by 137Cancer Genomics and DiagnosticsDNA Repair MechanismsEpigenetics and DNA Methylation

Mutational signature distribution varies with DNA replication timing and strand asymmetry

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Tomkova, Marketa, Tomek, Jakub, Kriaucionis, Skirmantas, Schuster-Böckler, Benjamin·2018·Genome Biology

Published version of a preprint

Abstract

BACKGROUND: DNA replication plays an important role in mutagenesis, yet little is known about how it interacts with other mutagenic processes. Here, we use somatic mutation signatures-each representing a mutagenic process-derived from 3056 patients spanning 19 cancer types to quantify the strand asymmetry of mutational signatures around replication origins and between early and late replicating regions. RESULTS: We observe that most of the detected mutational signatures are significantly correlated with the timing or direction of DNA replication. The properties of these associations are distinct for different signatures and shed new light on several mutagenic processes. For example, our results suggest that oxidative damage to the nucleotide pool substantially contributes to the mutational landscape of esophageal adenocarcinoma. CONCLUSIONS: Together, our results indicate an interaction between DNA replication, the associated damage repair, and most mutagenic processes.

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  1. [71]Tomkova M Tomek J Kriaucionis S Schuster-Bockler B Mutational signature distribution varies with DNA replication timing and strand asymmetry. Source code. Bitbucket 2018 PMC6130095 30201020

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Authors
Tomkova, M., Tomek, J., Kriaucionis, S., & Schuster-Böckler, B.
Affiliations
University of Oxford (GB)
Venue
Genome Biology
Published
2018-09-10
Volume
19
Issue
1
Pages
129-129
ISSN
  • 1465-6906 (ISSN-L)
  • 1474-760X
OpenAlex
W2890764841
Cited by
137
References
74
Citations by year
2026: 10 · 2025: 18 · 2024: 14 · 2023: 17 · 2022: 13 · 2021: 27 · 2020: 18 · 2019: 15 · 2018: 4 · 2017: 1
FWCI
4.82
Type
journal article
Language
en
Open access
Locations
  • Genome biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Ludwig Institute for Cancer Research (US)
  • Biotechnology and Biological Sciences Research Council (GB) (BB/M001873/1)
  • Engineering and Physical Sciences Research Council (GB) (EP/F500394/1)
  • Engineering and Physical Sciences Research Council (EP/F500394/1)
  • Ludwig Institute for Cancer Research
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
mutational signatures, DNA replication timing, origin of replication, somatic mutations, oxidative DNA damage, esophageal adenocarcinoma, DNA repair
MeSH terms
DNA Repair, Esophageal Neoplasms, Humans, Mutagens, Mutation, Neoplasms, Mutagenesis, DNA Replication Timing

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