APOBEC mutagenesis is a common process in normal human small intestine.

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dc.creatorWang, Yichen
dc.creatorRobinson, Philip S
dc.creatorCoorens, Tim HH
dc.creatorMoore, Luiza
dc.creatorLee-Six, Henry
dc.creatorNoorani, Ayesha
dc.creatorSanders, Mathijs A
dc.creatorJung, Hyunchul
dc.creatorKatainen, Riku
dc.creatorHeuschkel, Robert
dc.creatorBrunton-Sim, Roxanne
dc.creatorWeston, Robyn
dc.creatorRead, Debbie
dc.creatorNobbs, Beverley
dc.creatorFitzgerald, Rebecca C
dc.creatorSaeb-Parsy, Kourosh
dc.creatorMartincorena, Iñigo
dc.creatorCampbell, Peter J
dc.creatorRushbrook, Simon
dc.creatorZilbauer, Matthias
dc.creatorBuczacki, Simon James Alexander
dc.creatorStratton, Michael R
dc.date2023-02-16T15:00:23Z
dc.date2023-02-16T15:00:23Z
dc.date2023-02
dc.date2022-05-08
dc.date2023-02-16T15:00:22Z
dc.date.accessioned2026-08-03T02:03:32Z
dc.descriptionFunder: Core funding from the Wellcome Sanger Institute (Wellcome Trust, No. 206194).
dc.descriptionFunder: Wellcome PhD Studentship (Wellcome Trust, No. 206194)
dc.descriptionFunder: Wellcome Clinical PhD fellowship (Wellcome Trust, No. 206194)
dc.descriptionFunder: Pathological Society of Great Britain and Ireland; doi: https://doi.org/10.13039/501100000672
dc.descriptionFunder: Jean Shank/Pathological Society of Great Britain and Ireland Intermediate Clinical Fellowship(JSPS IF 2019 01)
dc.descriptionFunder: Finnish Center of Excellence Program 2018–2025, No. 312041
dc.descriptionFunder: NIHR Cambridge Biomedical Research Centre
dc.descriptionFunder: Core funding from The Pharsalia Trust.
dc.descriptionAPOBEC mutational signatures SBS2 and SBS13 are common in many human cancer types. However, there is an incomplete understanding of its stimulus, when it occurs in the progression from normal to cancer cell and the APOBEC enzymes responsible. Here we whole-genome sequenced 342 microdissected normal epithelial crypts from the small intestines of 39 individuals and found that SBS2/SBS13 mutations were present in 17% of crypts, more frequent than most other normal tissues. Crypts with SBS2/SBS13 often had immediate crypt neighbors without SBS2/SBS13, suggesting that the underlying cause of SBS2/SBS13 is cell-intrinsic. APOBEC mutagenesis occurred in an episodic manner throughout the human lifespan, including in young children. APOBEC1 mRNA levels were very high in the small intestine epithelium, but low in the large intestine epithelium and other tissues. The results suggest that the high levels of SBS2/SBS13 in the small intestine are collateral damage from APOBEC1 fulfilling its physiological function of editing APOB mRNA.
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dc.identifier1061-4036
dc.identifiers41588-022-01296-5
dc.identifier1296
dc.identifierhttps://www.repository.cam.ac.uk/handle/1810/346527
dc.identifier10.17863/CAM.93943
dc.identifier1546-1718
dc.identifier.urihttps://repo.dare.co.zw/handle/123456789/163056
dc.languageen
dc.publisherSpringer Science and Business Media LLC
dc.subjectArticle
dc.subject/631/208/212
dc.subject/631/114/2164
dc.subject/45
dc.subject/45/23
dc.subject/38/91
dc.subjectarticle
dc.titleAPOBEC mutagenesis is a common process in normal human small intestine.
dc.typeArticle

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