Association of a germline copy number polymorphism of APOBEC3A and APOBEC3B with burden of putative APOBEC-dependent mutations in breast cancer
Open accessAbstract
The somatic mutations in a cancer genome are the aggregate outcome of one or more mutational processes operative through the lifetime of the individual with cancer. Each mutational process leaves a characteristic mutational signature determined by the mechanisms of DNA damage and repair that constitute it. A role was recently proposed for the APOBEC family of cytidine deaminases in generating particular genome-wide mutational signatures and a signature of localized hypermutation called kataegis. A germline copy number polymorphism involving APOBEC3A and APOBEC3B, which effectively deletes APOBEC3B, has been associated with modestly increased risk of breast cancer. Here we show that breast cancers in carriers of the deletion show more mutations of the putative APOBEC-dependent genome-wide signatures than cancers in non-carriers. The results suggest that the APOBEC3A-APOBEC3B germline deletion allele confers cancer susceptibility through increased activity of APOBEC-dependent mutational processes, although the mechanism by which this increase in activity occurs remains unknown.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Case FBC070169 had a strong APOBEC substitution signature accounting for 94% of somatic mutations, but no APOBEC3A or APOBEC3B germline variants previously linked to this signature were found.
“Case FBC070169 had a strong APOBEC substitution signature accounting for 94% of the somatic mutations, yet there was no evidence of the APOBEC3A or APOBEC3B germline variants previously associated with this signature [15, 16].”
From Whole-genome sequencing reveals clinically relevant insights into the aetiology of familial breast cancers (2019) · cites this paper as [15]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 38 · Cited by 277
- Authors
- Nik-Zainal, S., Wedge, D. C., Alexandrov, L. B., Petljak, M., Butler, A. P., Bolli, N., Davies, H. R., Knappskog, S., Martin, S., Papaemmanuil, E., Ramakrishna, M., Shlien, A., Simonic, I., Xue, Y., Tyler-Smith, C., Campbell, P. J., & Stratton, M. R.
- Affiliations
- Wellcome Sanger Institute (GB)
- Haukeland University Hospital (NO)
- Hospital for Sick Children (CA)
- Cambridge University Hospitals NHS Foundation Trust (GB)
- University of Cambridge (GB)
- Corresponding author
- Alexandrov, Ludmil B
- Stratton, Michael R
- ORCID
- Venue
- Nature Genetics
- Published
- 2014-04-13
- Volume
- 46
- Issue
- 5
- Pages
- 487-491
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC4137149
- OpenAlex
- W1978469053
- Cited by
- 277
- References
- 38
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 10 · 2023: 16 · 2022: 19 · 2021: 20 · 2020: 24 · 2019: 35 · 2018: 22 · 2017: 35 · 2016: 37 · 2015: 29 · 2014: 10
- FWCI
- 11.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- Wellcome Trust (101126STRATTON, 100183, 088340, WT088340MA, WT100183MA, 098051)
- Academy of Medical Sciences (AMS-SGCL6-Bolli)
- European Commission (242006)
- 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
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- APOBEC3A, APOBEC3B, breast cancer, mutational signatures, kataegis, cytidine deaminase, cancer susceptibility, somatic mutations
- MeSH terms
- Breast Neoplasms, Cytidine Deaminase, Female, Genetic Markers, Humans, Proteins, Minor Histocompatibility Antigens, Mutagenesis, Sequence Deletion, Genetic Predisposition to Disease, DNA Copy Number Variations
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
