ArticleThe Journal of clinical investigation2014
Targeted p16(Ink4a) epimutation causes tumorigenesis and reduces survival in mice.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
48 citing papers in PubMed, 88 citations in OpenAlex.
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- The Pivotal Role of One-Carbon Metabolism in Neoplastic Progression During the Aging Process.Biomolecules · 2024Review
- Dietary Folate and Cofactors Accelerate Age-dependent p16 Epimutation to Promote Intestinal Tumorigenesis.Cancer research communications · 2024Article
- Non-pathogenic microbiota accelerate age-related CpG Island methylation in colonic mucosa.Epigenetics · 2023Article
- Functional characterization of age-dependent p16 epimutation reveals biological drivers and therapeutic targets for colorectal cancer.Journal of experimental & clinical cancer research : CR · 2023Article
- Prognostic value of the immunohistochemical score based on four markers in head and neck squamous cell carcinoma.Frontiers in immunology · 2023Article
- Metabolic rearrangements and intratumoral heterogeneity for immune response in hepatocellular carcinoma.Frontiers in immunology · 2023Review
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- DNA Methylation Biomarkers for Prediction of Response to Platinum-Based Chemotherapy: Where Do We Stand?Cancers · 2022Review
- Unique combinations of epigenetic modifiers synergistically impair the viability of the U87 glioblastoma cell line while exhibiting minor or moderate effects on normal stem cell growth.Medical oncology (Northwood, London, England) · 2022Article
- Epigenetic Changes and Functions in Pneumoconiosis.Oxidative medicine and cellular longevity · 2022Review
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- Epigenetics and sarcoidosis.European respiratory review : an official journal of the European Respiratory Society · 2021Review
- Multi-Omics Model Applied to Cancer Genetics.International journal of molecular sciences · 2021Review
- A CRISPR/Cas9-based method for targeted DNA methylation enables cancer initiation in B lymphocytes.Advanced genetics (Hoboken, N.J.) · 2021Article
- Genetic and Epigenetic Impact of Chronic Inflammation on Colon Mucosa Cells.Frontiers in genetics · 2021Article
- Review
- Site-Specific DNA Demethylation as a Potential Target for Cancer Epigenetic Therapy.Epigenetics insights · 2020Review
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Cancer has long been viewed as a genetic disease; however, epigenetic silencing as the result of aberrant promoter DNA methylation is frequently associated with cancer development, suggesting an epigenetic component to the disease. Nonetheless, it has remained unclear whether an epimutation (an aberrant change in epigenetic regulation) can induce tumorigenesis. Here, we exploited a functionally validated cis-acting regulatory element and devised a strategy to induce developmentally regulated genomic targeting of DNA methylation. We used this system to target DNA methylation within the p16(Ink4a) promoter in mice in vivo. Engineered p16(Ink4a) promoter hypermethylation led to transcriptional suppression in somatic tissues during aging and increased the incidence of spontaneous cancers in these mice. Further, mice carrying a germline p16(Ink4a) mutation in one allele and a somatic epimutation in the other had accelerated tumor onset and substantially shortened tumor-free survival. Taken together, these results provide direct functional evidence that p16(Ink4a) epimutation drives tumor formation and malignant progression and validate a targeted methylation approach to epigenetic engineering.
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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.