ArticleNature communications2024
Replication timing alterations are associated with mutation acquisition during breast and lung cancer evolution.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Decoding DNA metabolism and its clinical relevance through the lens of high-throughput sequencing assays.Medical review (2021) · 2026Review
- Neural Networks as Entropic Systems: Applications in Digital Pathology.bioRxiv : the preprint server for biology · 2026Article
- Reprogramming tumor immunity through APOBEC3s-mediated mutagenesis: from genome instability to immune checkpoint interactions.Frontiers in immunology · 2026Review
- KCTD10 as a selective cancer dependency from transcription-replication conflicts (TRCs).Ageing and cancer research & treatment · 2026Article
- Spatial mapping of DNA synthesis reveals dynamics and geometry of human replication nanostructures.The EMBO journal · 2025Article
- Integration of multi-omics approaches in exploring intra-tumoral heterogeneity.Cancer cell international · 2025Review
- Unravelling single-cell DNA replication timing dynamics using machine learning reveals heterogeneity in cancer progression.Nature communications · 2025Article
- Single-cell genomics breaks new ground in cell cycle detection.Nature genetics · 2025Article
- Characterizing the evolutionary dynamics of cancer proliferation in single-cell clones with SPRINTER.Nature genetics · 2025Article
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
During each cell cycle, the process of DNA replication timing is tightly regulated to ensure the accurate duplication of the genome. The extent and significance of alterations in this process during malignant transformation have not been extensively explored. Here, we assess the impact of altered replication timing (ART) on cancer evolution by analysing replication-timing sequencing of cancer and normal cell lines and 952 whole-genome sequenced lung and breast tumours. We find that 6%-18% of the cancer genome exhibits ART, with regions with a change from early to late replication displaying an increased mutation rate and distinct mutational signatures. Whereas regions changing from late to early replication contain genes with increased expression and present a preponderance of APOBEC3-mediated mutation clusters and associated driver mutations. We demonstrate that ART occurs relatively early during cancer evolution and that ART may have a stronger correlation with mutation acquisition than alterations in chromatin structure.
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Registered trials
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