ArticleNature2019
Age-related remodelling of oesophageal epithelia by mutated cancer drivers.
Article in Nature, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 385 papers.
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Who cites it
385 citing papers in PubMed, 633 citations in OpenAlex.
- Comprehensive Genomic Analysis of Normal and Cancer Cells Elucidates the Elevated Mutational Burden in Cancer.Cancer research · 2026Article
- Cancer treatment alters mutant selection in normal esophagus.Nature genetics · 2026Article
- A single-cell lens into the co-evolution of genotypes and phenotypes in cancer.Nature reviews. Cancer · 2026Review
- High-grade serous ovarian cancer is associated with increased TP53 mutation burden in uterine lavage.NPJ precision oncology · 2026Article
- Understanding the somatic evolution of metabolic traits.Nature metabolism · 2026Article
- Context-dependent selection sculpts mutational landscapes in the normal lung.Research square · 2026Article
- Age distinguishes selection from causation in cancer genomes.Nature genetics · 2026Article
- Germline mutations and somatic mosaicism in steatotic liver diseases and related liver carcinogenesis.Nature reviews. Gastroenterology & hepatology · 2026Review
- Polyclonal evolution of lymphoproliferative disorders in XLP1.Journal of human immunity · 2026Article
- Article
- Esophageal cancer: from pathogenesis to precision therapies.Signal transduction and targeted therapy · 2026Review
- Enrichment of T: A→A: T substitutions in the TP53 gene in esophageal carcinoma with high Fusobacterium burden.Scientific reports · 2026Article
- Harnessing genomics for early cancer detection, risk stratification and prevention.Nature genetics · 2026Review
- Genotype-to-Phenotype Mapping of Somatic Clonal Mosaicism via Single-Cell Co-Capture of DNA Mutations and mRNA Transcripts.Cancer discovery · 2026Article
- Tumour promotion through the lens of evolution.Nature · 2026Review
- Somatic mutations and clonal evolution in normal tissues and cancer development.Experimental & molecular medicine · 2026Review
- Review
- Genetic risk stratification and preventive strategies for double primary HNSCC and ESCC: a single-center cohort study.Esophagus : official journal of the Japan Esophageal Society · 2026Article
- Review
- Telomere Crisis Shapes Cancer Evolution.Cold Spring Harbor perspectives in biology · 2026Review
325 more citing papers are in PubMed but not listed here.
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Authors and funding
40 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clonal expansion in aged normal tissues has been implicated in the development of cancer. However, the chronology and risk dependence of the expansion are poorly understood. Here we intensively sequence 682 micro-scale oesophageal samples and show, in physiologically normal oesophageal epithelia, the progressive age-related expansion of clones that carry mutations in driver genes (predominantly NOTCH1), which is substantially accelerated by alcohol consumption and by smoking. Driver-mutated clones emerge multifocally from early childhood and increase their number and size with ageing, and ultimately replace almost the entire oesophageal epithelium in the extremely elderly. Compared with mutations in oesophageal cancer, there is a marked overrepresentation of NOTCH1 and PPM1D mutations in physiologically normal oesophageal epithelia; these mutations can be acquired before late adolescence (as early as early infancy) and significantly increase in number with heavy smoking and drinking. The remodelling of the oesophageal epithelium by driver-mutated clones is an inevitable consequence of normal ageing, which-depending on lifestyle risks-may affect cancer development.
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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.