Replication-associated mechanisms contribute to an increased CpG > TpG mutation burden in mismatch repair-deficient cancers
There is a CpG > TpG and SBS1 excess specific to dMutSα MMRd tumours, consistent with previous reports, and we find a general increase in somatic C > T mutations. Contrary to some other studies, the similar leading replication strand bias in both dMutSα and dMutLα tumours indicates that at least some of the excess CpG > TpG mutations arise via DNA replication errors, and not primarily via the replication-independent deamination of 5'-methylcytosine.
Authors
- Claire Palles (ORCID: https://orcid.org/0000-0002-9670-2263)
- Juan Fernández‐Tajes (ORCID: https://orcid.org/0000-0003-1515-2421)
- Ignacio Soriano (ORCID: https://orcid.org/0000-0002-7928-3511)
- Andreas Gruber (ORCID: https://orcid.org/0000-0001-7664-4257)
- S. Thorn (ORCID: https://orcid.org/0000-0002-9962-9356)
- Ian Tomlinson (ORCID: https://orcid.org/0000-0003-3037-1470)
- Güler Gül
- Kitty Sherwood (ORCID: https://orcid.org/0009-0007-4055-607X)
- Ioannis Kafetzopoulos (ORCID: https://orcid.org/0000-0001-5948-3455)
- Sara Galavotti (ORCID: https://orcid.org/0000-0002-1240-0963)
- David N. Church (ORCID: https://orcid.org/0000-0002-4617-962X)
- Ben Kinnersley (ORCID: https://orcid.org/0000-0003-1783-6296)
- Duncan Sproul (ORCID: https://orcid.org/0000-0001-6168-4563)
- Anna Frangou (ORCID: https://orcid.org/0000-0001-6990-2756)
- Joseph C. Ward (ORCID: https://orcid.org/0009-0000-8319-6464)
- Joost Scheffers
Institutions
- Centre for Human Genetics (GB)
- University of Konstanz (DE)
- Leiden University Medical Center (NL)
- Western General Hospital (GB)
- Edinburgh Cancer Research (GB)
- John Radcliffe Hospital (GB)
- University of Oxford (GB)
- CRUK/MRC Oxford Institute for Radiation Oncology (GB)
- Cancer Research UK Manchester Institute (GB)
- Cancer Research UK Clinical Trials Unit (GB)
- Health Data Research UK (GB)
- Oxford BioMedica (United Kingdom) (GB)
- CRUK Lung Cancer Centre of Excellence (GB)
- Max Planck Institute of Molecular Cell Biology and Genetics (DE)
- University College London (GB)
- University of Birmingham (GB)
- University of Edinburgh (GB)
Publication Details
- Journal
- Genome Medicine
- Published
- 2025-08-25
- DOI
- https://doi.org/10.1186/s13073-025-01525-6
- Primary Topic
- Genetic factors in colorectal cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Wellcome Trust
- Cancer Research UK
- National Institute for Health and Care Research
- Department of Health and Social Care
- Medical Research Council