ArticleClinical epigenetics2021
Evaluation of global and intragenic hypomethylation in colorectal adenomas improves patient stratification and colorectal cancer risk prediction.
Article in Clinical epigenetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 32 citations in OpenAlex.
- Targeting molecular and genetic pathways driving tumorigenesis for precision therapy in colorectal cancer.Cancer biology & therapy · 2026Review
- Global Hypomethylation in Cell-Free DNA Enables Noninvasive Colorectal Cancer Screening: Results from a Retrospective Validation Study.Computational and structural biotechnology journal · 2026Article
- Genome-wide profiling of unmodified DNA using methyltransferase-directed tagging and enrichment.Cell reports methods · 2025Article
- Aging-Related Mechanisms Underlying Carcinogenesis: Therapeutic Opportunities.Aging and disease · 2025Review
- Plasmonic Molecular Entrapment for Label-Free Methylated DNA Detection and Machine-Learning Assisted Quantification.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The role of physical activity and epigenetic changes in colorectal cancer prevention.Cancer cell international · 2025Review
- Construction and analysis of the invasive prediction model for pulmonary nodules: based on clinical, CT image and DNA methylation characteristics.Journal of thoracic disease · 2025Article
- The Role of DNA Methylation in Gastrointestinal Disease: An Expanded Review of Malignant and Nonmalignant Gastrointestinal Diseases.Gastroenterology · 2025Review
- IncreasedMolecular & cellular oncology · 2025Article
- The role of diet in cancer: the potential of shaping public policy and clinical outcomes in the UK.Genes & nutrition · 2024Review
- Article
- CRISPR/dCAS9-mediated DNA demethylation screen identifies functional epigenetic determinants of colorectal cancer.Clinical epigenetics · 2023Article
- The Importance of the Immune System and Molecular Cell Signaling Pathways in the Pathogenesis and Progression of Lung Cancer.International journal of molecular sciences · 2023Review
- Gene body methylation in cancer: molecular mechanisms and clinical applications.Clinical epigenetics · 2022Review
- Liquid biopsies based on DNA methylation as biomarkers for the detection and prognosis of lung cancer.Clinical epigenetics · 2022Review
- Article
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAberrant DNA hypomethylation of the long interspersed nuclear elements (LINE-1 or L1) has been recognized as an early event of colorectal transformation. Simultaneous genetic and epigenetic analysis of colorectal adenomas may be an effective and rapid strategy to identify key biological features leading to accelerated colorectal tumorigenesis. In particular, global and/or intragenic LINE-1 hypomethylation of adenomas may represent a helpful tool for improving colorectal cancer (CRC) risk stratification of patients after surgical removal of polyps. To verify this hypothesis, we analyzed a cohort of 102 adenomas derived from 40 high-risk patients (who developed CRC in a post-polypectomy of at least one year) and 43 low-risk patients (who did not develop CRC in a post-polypectomy of at least 5 years) for their main pathological features, the presence of hotspot variants in driver oncogenes (KRAS, NRAS, BRAF and PIK3CA), global (LINE-1) and intragenic (L1-MET) methylation status.
resultsIn addition to a significantly higher adenoma size and an older patients' age, adenomas from high-risk patients were more hypomethylated than those from low-risk patients for both global and intragenic LINE-1 assays. DNA hypomethylation, measured by pyrosequencing, was independent from other parameters, including the presence of oncogenic hotspot variants detected by mass spectrometry. Combining LINE-1 and L1-MET analyses and profiling the samples according to the presence of at least one hypomethylated assay improved the discrimination between high and low risk lesions (p = 0.005). Remarkably, adenomas with at least one hypomethylated assay identified the patients with a significantly (p < 0.001) higher risk of developing CRC. Multivariable analysis and logistic regression evaluated by the ROC curves proved that methylation status was an independent variable improving cancer risk prediction (p = 0.02).
conclusionsLINE-1 and L1-MET hypomethylation in colorectal adenomas are associated with a higher risk of developing CRC. DNA global and intragenic hypomethylation are independent markers that could be used in combination to successfully improve the stratification of patients who enter a colonoscopy surveillance program.
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