Nature Communications (Jul 2022)
Inherited MUTYH mutations cause elevated somatic mutation rates and distinctive mutational signatures in normal human cells
- Philip S. Robinson,
- Laura E. Thomas,
- Federico Abascal,
- Hyunchul Jung,
- Luke M. R. Harvey,
- Hannah D. West,
- Sigurgeir Olafsson,
- Bernard C. H. Lee,
- Tim H. H. Coorens,
- Henry Lee-Six,
- Laura Butlin,
- Nicola Lander,
- Rebekah Truscott,
- Mathijs A. Sanders,
- Stefanie V. Lensing,
- Simon J. A. Buczacki,
- Rogier ten Hoopen,
- Nicholas Coleman,
- Roxanne Brunton-Sim,
- Simon Rushbrook,
- Kourosh Saeb-Parsy,
- Fiona Lalloo,
- Peter J. Campbell,
- Iñigo Martincorena,
- Julian R. Sampson,
- Michael R. Stratton
Affiliations
- Philip S. Robinson
- Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute
- Laura E. Thomas
- Institute of Life Science, Swansea University
- Federico Abascal
- Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute
- Hyunchul Jung
- Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute
- Luke M. R. Harvey
- Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute
- Hannah D. West
- Institute of Medical Genetics, Division of Cancer and Genetics, Cardiff University School of Medicine
- Sigurgeir Olafsson
- Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute
- Bernard C. H. Lee
- Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute
- Tim H. H. Coorens
- Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute
- Henry Lee-Six
- Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute
- Laura Butlin
- Institute of Medical Genetics, Division of Cancer and Genetics, Cardiff University School of Medicine
- Nicola Lander
- Institute of Medical Genetics, Division of Cancer and Genetics, Cardiff University School of Medicine
- Rebekah Truscott
- Institute of Medical Genetics, Division of Cancer and Genetics, Cardiff University School of Medicine
- Mathijs A. Sanders
- Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute
- Stefanie V. Lensing
- Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute
- Simon J. A. Buczacki
- Nuffield Department of Surgical Sciences, Medical Sciences Division, University of Oxford
- Rogier ten Hoopen
- Department of Oncology, University of Cambridge
- Nicholas Coleman
- Department of Pathology, University of Cambridge
- Roxanne Brunton-Sim
- Norfolk and Norwich University Hospital
- Simon Rushbrook
- Norfolk and Norwich University Hospital
- Kourosh Saeb-Parsy
- Department of Surgery, University of Cambridge
- Fiona Lalloo
- Manchester Centre for Genomic Medicine, Saint Mary’s Hospital
- Peter J. Campbell
- Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute
- Iñigo Martincorena
- Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute
- Julian R. Sampson
- Institute of Medical Genetics, Division of Cancer and Genetics, Cardiff University School of Medicine
- Michael R. Stratton
- Cancer, Ageing and Somatic Mutation (CASM), Wellcome Sanger Institute
- DOI
- https://doi.org/10.1038/s41467-022-31341-0
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 12
Abstract
Inherited mutations in MUTYH have been shown to predispose patients to colorectal cancers. Here, the authors show that MUTYH mutations lead to an increased somatic base substitution mutation rate in normal intestinal epithelial cells, which is the likely cause for the increased cancer risk.
