ArticleGenome research2016
Enhancer methylation dynamics contribute to cancer plasticity and patient mortality.
Article in Genome research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 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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Who cites it
75 citing papers in PubMed, 112 citations in OpenAlex.
- Epigenetic reprogramming of lineage switching in cancer.FEBS letters · 2026Review
- Metastasis-associated DNA methylation alterations persist after accounting for immune and stromal cell heterogeneity in primary colorectal tumors.Research square · 2026Article
- Epigenetic entropy, socioeconomic differences, and health and lifespan in the Women's Health Initiative.Clinical epigenetics · 2026Article
- DNA methylation profiles aid to identify putative genome activation histories along lymphomagenesis.NAR genomics and bioinformatics · 2026Article
- Article
- Systematic analysis of functional genetic and epigenetic variants in colorectal cancer.Science advances · 2026Article
- Genetic evolution of keratinocytes to cutaneous squamous cell carcinoma.Nature communications · 2025Article
- Genome-wide profiling of unmodified DNA using methyltransferase-directed tagging and enrichment.Cell reports methods · 2025Article
- Epigenetic Modulation and Brain Function in Parkinson's Disease: The Role of Exercise Alone or Combined With Polyphenols.Food science & nutrition · 2025Review
- Comprehensive multi-omics pan-cancer analysis revealed EGFLAM as a potential prognostic and immune infiltration-associated biomarker.BMC cancer · 2025Article
- Association of Intergenic and IntragenicInternational journal of molecular sciences · 2025Article
- Cell-type-specific subtyping of epigenomes improves prognostic stratification of cancer.Genome medicine · 2025Article
- Genome-wide DNA methylation regulation analysis provides novel insights on post-radiation breast cancer.Scientific reports · 2025Article
- Super-enhancer DNA methylation in cancer: the mechanism of action and therapeutic directions.Frontiers in oncology · 2025Review
- DNA Methylation Classes of Stage II and III Primary Melanomas and Their Clinical and Prognostic Significance.JCO precision oncology · 2024Article
- Methylation of microRNA genes and its effect on secondary xylem development of stem in poplar.The plant genome · 2024Article
- Epigenetic Alteration in Colorectal Cancer: Potential Diagnostic and Prognostic Implications.International journal of molecular sciences · 2024Review
- Epigenetic control of the vicious cycle.Journal of bone oncology · 2024Article
- Unveiling DNA methylation: early diagnosis, risk assessment, and therapy for endometrial cancer.Frontiers in oncology · 2024Review
- Epigenomic analysis reveals a unique DNA methylation program of metastasis-competent circulating tumor cells in colorectal cancer.Scientific reports · 2023Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During development, enhancers play pivotal roles in regulating gene expression programs; however, their involvement in cancer progression has not been fully characterized. We performed an integrative analysis of DNA methylation, RNA-seq, and small RNA-seq profiles from thousands of patients, including 25 diverse primary malignances and seven body sites of metastatic melanoma. We found that enhancers are consistently the most differentially methylated regions (DMR) as cancer progresses from normal to primary tumors and then to metastases, compared to other genomic features. Remarkably, identification of enhancer DMRs (eDMRs) enabled classification of primary tumors according to physiological organ systems, and in metastasis eDMRs are the most correlated with patient outcome. To further understand the eDMR role in cancer progression, we developed a model to predict genes and microRNAs that are regulated by enhancer and not promotor methylation, which shows high accuracy with chromatin architecture methods and was experimentally validated. Interestingly, among all metastatic melanoma eDMRs, the most correlated with patient survival were eDMRs that "switched" their methylation patterns back and forth between normal, primary, and metastases and target cancer drivers, e.g., KIT We further demonstrated that eDMR target genes were modulated in melanoma by the bone metastasis microenvironment, suggesting that eDMRs respond to microenvironmental cues in metastatic niches. Our findings that aberrant methylation in cancer cells mostly affects enhancers, which contribute to tumor progression and cancer cell plasticity, will facilitate development of epigenetic anticancer approaches.
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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.