ArticleNature genetics2023
Notch1 mutations drive clonal expansion in normal esophageal epithelium but impair tumor growth.
Article in Nature genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 110 citations in OpenAlex.
- Cancer treatment alters mutant selection in normal esophagus.Nature genetics · 2026Article
- The Evolution of Polyclonal Competition in Aging Hematopoiesis.Cancer discovery · 2026Article
- Chemically induced skin tumors arise from long-lived stem cells of the upper hair follicle.Science (New York, N.Y.) · 2026Article
- Prognostic significance of positive margin-informed tumor status in esophageal squamous cell carcinoma using next-generation sequencing.The oncologist · 2026Article
- Evolving patterns of co-mutations from tumor initiation to metastatic progression.Nature genetics · 2026Article
- Paired mutation calling and spatial transcriptomics identify cellular neighborhoods associated with the neoplastic outcome of mouse colitis.Nature genetics · 2026Article
- Age identifies cancer drivers hidden within the genome.Nature genetics · 2026Article
- Age distinguishes selection from causation in cancer genomes.Nature genetics · 2026Article
- Spatiotemporal Transcriptomic Dissection Uncovers Age-Dependent Deceleration of Esophageal Cell Differentiation.bioRxiv : the preprint server for biology · 2026Article
- Accelerating discovery of cancer causes for prevention in the era of rising early-onset cancers.Cell · 2026Review
- Esophageal cancer: from pathogenesis to precision therapies.Signal transduction and targeted therapy · 2026Review
- Tumour promotion through the lens of evolution.Nature · 2026Review
- HMGA2 promotes hepatocellular carcinoma progression by regulating tumor-associated macrophage via Notch1/CCL2 signaling.Molecular and cellular biochemistry · 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
- Somatic mutations and clonal evolution in normal tissues and cancer development.Experimental & molecular medicine · 2026Review
- Review
- How somatic evolution affects health.Nature ecology & evolution · 2026Article
- Cell cycle criticality as a mechanism for robust cell population control.Molecular systems biology · 2026Article
- The dual role of the Notch signaling pathway in digestive system cancers.European journal of medical research · 2026Review
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
Abstract
NOTCH1 mutant clones occupy the majority of normal human esophagus by middle age but are comparatively rare in esophageal cancers, suggesting NOTCH1 mutations drive clonal expansion but impede carcinogenesis. Here we test this hypothesis. Sequencing NOTCH1 mutant clones in aging human esophagus reveals frequent biallelic mutations that block NOTCH1 signaling. In mouse esophagus, heterozygous Notch1 mutation confers a competitive advantage over wild-type cells, an effect enhanced by loss of the second allele. Widespread Notch1 loss alters transcription but has minimal effects on the epithelial structure and cell dynamics. In a carcinogenesis model, Notch1 mutations were less prevalent in tumors than normal epithelium. Deletion of Notch1 reduced tumor growth, an effect recapitulated by anti-NOTCH1 antibody treatment. Notch1 null tumors showed reduced proliferation. We conclude that Notch1 mutations in normal epithelium are beneficial as wild-type Notch1 favors tumor expansion. NOTCH1 blockade may have therapeutic potential in preventing esophageal squamous cancer.
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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.