Comparison between germline and somatic loss-of-function <i>RNF43</i> mutations reveals different genotype-phenotype associations and provides insights into the genetic mechanisms of colorectal tumourigenesis
<i>RNF43</i> is a CRC predisposition gene, but risks are moderate, the reported polyposis phenotype is often absent and molecular phenocopies can occur. N-terminal germline <i>RNF43</i> variants confer higher risk, although weak effects of C-terminal variants cannot be excluded. Genetic testing and patient management should incorporate these factors.
Authors
- Sulochana Omwenga (ORCID: https://orcid.org/0000-0003-2848-429X)
- Sujata Biswas (ORCID: https://orcid.org/0000-0002-0700-7286)
- Jeremy P. Cheadle (ORCID: https://orcid.org/0000-0001-9453-8458)
- S J Leedham
- Juan Fernández‐Tajes (ORCID: https://orcid.org/0000-0003-1515-2421)
- S. Thorn (ORCID: https://orcid.org/0000-0002-9962-9356)
- Dmitri Mouradov (ORCID: https://orcid.org/0000-0001-8149-816X)
- Luke Freeman-Mills (ORCID: https://orcid.org/0000-0001-7868-8528)
- Sara Galavotti (ORCID: https://orcid.org/0000-0002-1240-0963)
- Silvia Salatino (ORCID: https://orcid.org/0000-0003-1286-3076)
- Helen Curley (ORCID: https://orcid.org/0000-0002-0782-4964)
- Connor E. Woolley (ORCID: https://orcid.org/0000-0002-0770-6968)
- James E. East (ORCID: https://orcid.org/0000-0001-8035-3700)
- Nathalie Feeley (ORCID: https://orcid.org/0000-0003-0124-6398)
- M. Sieber Oliver
- Laura Chegwidden
- Maughan Ts
- Edward Arbe-Barnes
- Roland Arnold
- Claire Palles
- Anshita Goel
- Ian Tomlinson
- Lai Mun Wang
Institutions
- Centre for Human Genetics (GB)
- The University of Melbourne (AU)
- University of Basel (CH)
- Walter and Eliza Hall Institute of Medical Research (AU)
- Changi General Hospital (SG)
- University Hospital of Basel (CH)
- Edinburgh Cancer Research (GB)
- National Institute for Health and Care Research (GB)
- University of Oxford (GB)
- Oxford BioMedica (United Kingdom) (GB)
- NIHR Birmingham Biomedical Research Centre (GB)
- Cardiff University (GB)
- University of Birmingham (GB)
Publication Details
- Journal
- Gut
- Published
- 2025-12-24
- DOI
- https://doi.org/10.1136/gutjnl-2025-337030
- Primary Topic
- Genetic factors in colorectal cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Wellcome Trust
- Bowel Cancer UK
- Cancer Research UK
- National Institute for Health and Care Research
- Department of Health and Social Care
- University of Birmingham
- Medical Research Council
- NIHR Oxford Biomedical Research Centre
- Birmingham Biomedical Research Centre