ArticleNature communications2022
Inherited MUTYH mutations cause elevated somatic mutation rates and distinctive mutational signatures in normal human cells.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 59 citations in OpenAlex.
- Dynamics of mutators of arbitrary dominance in humans.bioRxiv : the preprint server for biology · 2026Article
- The DNA damage response and cancer immunotherapy.Nature reviews. Cancer · 2026Review
- Motif-centered analyses reveal universal and tissue-specific mutagenic mechanisms operating in the human body.NAR cancer · 2026Article
- 8oxoG:A Is Structurally Accommodated in the Nucleosome Core Particle, Yet Inaccessible to MUTYH-Initiated DNA Repair.Biomolecules · 2026Article
- Biochemical, structural and mutational landscapes of base excision repair enzymes and cancer: from atomic resolution to tumor signatures.International journal of radiation biology · 2026Review
- A sibling study of variation in parental mutation rates.bioRxiv : the preprint server for biology · 2026Article
- Motif-Centered Analyses Reveal Universal and Tissue-Specific Mutagenic Mechanisms Operating in the Human Body.bioRxiv : the preprint server for biology · 2026Article
- Functional Profiling of DNA Repair Pathways in Lung Cancer Patients Uncovers Radiotherapy-Induced and Cancer-Associated Alterations in Oxidative Lesion Repair.medRxiv : the preprint server for health sciences · 2026Article
- Pathogenic germline variants identified in pNEN patients during genetic testing.Endocrine oncology (Bristol, England) · 2026Article
- Reconstructing the lifelong history of cells and tissues via somatic mutation analysis.Cellular and molecular life sciences : CMLS · 2025Review
- Comprehensive Measurement of Inter-Individual Variation in DNA Repair Capacity in Healthy Individuals.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The evolution of cancer and ageing: a history of constraint.Nature reviews. Cancer · 2025Review
- UVA-induced DNA damage and mutations in human melanocytes: relevance for melanoma mutations.Nucleic acids research · 2025Article
- Saturation mapping of MUTYH variant effects using DNA repair reporters.American journal of human genetics · 2025Article
- Unlocking the chemistry facilitated by enzymes that process nucleic acids using quantum mechanical and combined quantum mechanics-molecular mechanics techniques.Pure and applied chemistry. Chimie pure et appliquee · 2025Review
- Chemotherapy and the somatic mutation burden of sperm.JCI insight · 2025Article
- Human-Specific Organization of Proliferation and Stemness in Squamous Epithelia: A Comparative Study to Elucidate Differences in Stem Cell Organization.International journal of molecular sciences · 2025Article
- Colorectal carcinogenesis in the Lynch syndromes and familial adenomatous polyposis: trigger events and downstream consequences.Hereditary cancer in clinical practice · 2025Review
- Contributing factors to the oxidation-induced mutational landscape in human cells.Nature communications · 2024Article
- A maternal germline mutator phenotype in a family affected by heritable colorectal cancer.Genetics · 2024Article
Corrections and comments
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Authors and funding
26 authors at 9 institutions in 4 countries.
Funding
Abstract
Cellular DNA damage caused by reactive oxygen species is repaired by the base excision repair (BER) pathway which includes the DNA glycosylase MUTYH. Inherited biallelic MUTYH mutations cause predisposition to colorectal adenomas and carcinoma. However, the mechanistic progression from germline MUTYH mutations to MUTYH-Associated Polyposis (MAP) is incompletely understood. Here, we sequence normal tissue DNAs from 10 individuals with MAP. Somatic base substitution mutation rates in intestinal epithelial cells were elevated 2 to 4-fold in all individuals, except for one showing a 31-fold increase, and were also increased in other tissues. The increased mutation burdens were of multiple mutational signatures characterised by C > A changes. Different mutation rates and signatures between individuals are likely due to different MUTYH mutations or additional inherited mutations in other BER pathway genes. The elevated base substitution rate in normal cells likely accounts for the predisposition to neoplasia in MAP. Despite ubiquitously elevated mutation rates, individuals with MAP do not display overt evidence of premature ageing. Thus, accumulation of somatic mutations may not be sufficient to cause the global organismal functional decline of ageing.
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