ArticleJournal of the Royal Society, Interface2019
Relating evolutionary selection and mutant clonal dynamics in normal epithelia.
Article in Journal of the Royal Society, Interface, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- Stem cell competition.Current topics in developmental biology · 2026Review
- Large-scale single-cell phylogenetic mapping of clonal evolution in the human aging esophagus.bioRxiv : the preprint server for biology · 2025Article
- Understanding the impact of mitochondrial DNA mutations on aging and carcinogenesis (Review).International journal of molecular medicine · 2025Review
- Mutational Landscapes of Normal Skin and Their Potential Implications in the Development of Skin Cancer: A Comprehensive Narrative Review.Journal of clinical medicine · 2024Review
- Agent-based methods facilitate integrative science in cancer.Trends in cell biology · 2023Review
- Homeostasis limits keratinocyte evolution.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Somatic Mutation: What Shapes the Mutational Landscape of Normal Epithelia?Cancer discovery · 2022Review
- Lineage tracing in human tissues.The Journal of pathology · 2022Review
- Article
- Simulations reveal that different responses to cell crowding determine the expansion ofJournal of the Royal Society, Interface · 2021Article
- Selection of Oncogenic Mutant Clones in Normal Human Skin Varies with Body Site.Cancer discovery · 2021Article
- A Scarless Healing Tale: Comparing Homeostasis and Wound Healing of Oral Mucosa With Skin and Oesophagus.Frontiers in cell and developmental biology · 2021Review
- Spatial competition shapes the dynamic mutational landscape of normal esophageal epithelium.Nature genetics · 2020Article
- Article
- Outcompeting p53-Mutant Cells in the Normal Esophagus by Redox Manipulation.Cell stem cell · 2019Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Cancer develops from mutated cells in normal tissues. Whether somatic mutations alter normal cell dynamics is key to understanding cancer risk and guiding interventions to reduce it. An analysis of the first incomplete moment of size distributions of clones carrying cancer-associated mutations in normal human eyelid skin gives a good fit with neutral drift, arguing mutations do not affect cell fate. However, this suggestion conflicts with genetic evidence in the same dataset that argues for strong positive selection of a subset of mutations. This implies cells carrying these mutations have a competitive advantage over normal cells, leading to large clonal expansions within the tissue. In the normal epithelium, clone growth is constrained by the limited size of the proliferating compartment and competition with surrounding cells. We show that if these factors are taken into account, the first incomplete moment of the clone size distribution is unable to exclude non-neutral behaviour. Furthermore, experimental factors can make a non-neutral clone size distribution appear neutral. We validate these principles with a new experimental dataset showing that when experiments are appropriately designed, the first incomplete moment can be a useful indicator of non-neutral competition. Finally, we discuss the complex relationship between mutant clone sizes and genetic selection.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.