Genetic variation at 11q23.1 confers colorectal cancer risk by dysregulation of colonic tuft cell transcriptional activator <i>POU2AF2</i>
We demonstrate that genotype at rs3087967 controls a portfolio of genes through misregulation of <i>POU2AF2. POU2AF2</i> is the primary transcriptional activator of tuft cells with a tumour suppressive role in mouse models. We therefore implicate tuft cells as having a key tumour-protective role in the large bowel epithelium.
Authors
- Kevin Donnelly (ORCID: https://orcid.org/0000-0001-7633-9113)
- Susan M. Farrington (ORCID: https://orcid.org/0000-0001-5955-7389)
- Li Yin Ooi
- James P. Blackmur (ORCID: https://orcid.org/0000-0001-7267-837X)
- Vidya Rajasekaran (ORCID: https://orcid.org/0000-0002-3501-9321)
- Malcolm G. Dunlop (ORCID: https://orcid.org/0000-0002-3033-5851)
- Bradley T. Harris (ORCID: https://orcid.org/0000-0001-9585-1016)
- Richard S. Houlston (ORCID: https://orcid.org/0000-0002-5268-0242)
- Marion Walker (ORCID: https://orcid.org/0009-0005-6937-5745)
- Ceres Fernández–Rozadilla (ORCID: https://orcid.org/0000-0001-7330-4804)
- P G Vaughan-Shaw (ORCID: https://orcid.org/0000-0002-9790-6882)
- Graeme R. Grimes (ORCID: https://orcid.org/0000-0002-3106-5996)
- Ian Tomlinson (ORCID: https://orcid.org/0000-0003-3037-1470)
- Kevin Myant (ORCID: https://orcid.org/0000-0001-8017-1093)
- Claire Smillie (ORCID: https://orcid.org/0000-0003-1350-2301)
- Philip Law (ORCID: https://orcid.org/0000-0001-9663-4611)
- Ruby Tamara Osborn (ORCID: https://orcid.org/0000-0002-3222-1743)
- Marion Bacou
- Alison Meynert (ORCID: https://orcid.org/0000-0001-5839-1751)
- Morven Allan
- Maria Timofeeva (ORCID: https://orcid.org/0000-0002-2503-4253)
- Edward Esiri-Bloom (ORCID: https://orcid.org/0000-0003-0685-2629)
- S. Reid (ORCID: https://orcid.org/0000-0002-9728-3507)
- Farhat VN Din
Institutions
- Institute of Cancer Research (GB)
- National University of Singapore (SG)
- University of Southern Denmark (DK)
- Wellcome Sanger Institute (GB)
- Edinburgh Cancer Research (GB)
- University of Oxford (GB)
- Instituto de Investigación Sanitaria de Santiago (ES)
- Institute of Genetics and Cancer (GB)
- University of Edinburgh (GB)
Publication Details
- Journal
- Gut
- Published
- 2024-11-28
- DOI
- https://doi.org/10.1136/gutjnl-2024-332121
- Citations
- 6
- Primary Topic
- Cancer-related molecular mechanisms research
- Type
- article
- Field-Weighted Citation Impact
- 1.71
Funders
- Cancer Research UK
- Medical Research Council