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Updated: Jun 20, 2025
08:06
Genome-wide Determination of Mammalian Replication Timing by DNA Content Measurement
Published on: January 19, 2017
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Replication timing alterations are associated with mutation acquisition during breast and lung cancer evolution
Michelle Dietzen1,2,3, Haoran Zhai1,3, Olivia Lucas1,3,4,5
1Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
Nature Communications
|July 17, 2024
Summary
Altered replication timing (ART) affects 6%-18% of the cancer genome, influencing mutation rates and gene expression. ART appears early in cancer evolution and strongly correlates with mutation acquisition.
Area of Science:
- Genomics
- Cancer Biology
- Molecular Biology
Background:
- DNA replication timing is crucial for accurate genome duplication.
- The role of altered replication timing (ART) in cancer development is not well understood.
Purpose of the Study:
- To investigate the impact of ART on cancer evolution.
- To analyze replication timing changes in cancer and normal cell lines and tumors.
Main Methods:
- Replication-timing sequencing of cancer and normal cell lines.
- Whole-genome sequencing of 952 lung and breast tumors.
Main Results:
- 6%-18% of the cancer genome shows ART.
- Early-to-late replication shifts increase mutation rates and alter mutational signatures.
- Late-to-early replication shifts are linked to increased gene expression, APOBEC3 mutations, and driver mutations.
Conclusions:
- ART is an early event in cancer evolution.
- ART correlates more strongly with mutation acquisition than chromatin structure alterations.
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