ArticleInternational journal of cancer2008
LINE-1 hypomethylation is inversely associated with microsatellite instability and CpG island methylator phenotype in colorectal cancer.
Article in International journal of cancer, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 167 papers, 2 of them syntheses that pooled it.
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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
167 citing papers in PubMed, 2 syntheses or guidelines pooled it, 262 citations in OpenAlex.
- Epigenetic Biomarkers in Colorectal Cancer Patients Receiving Adjuvant or Neoadjuvant Therapy: A Systematic Review of Epidemiological Studies.International journal of molecular sciences · 2019Pooled it
- The role of LINE-1 methylation in predicting survival among colorectal cancer patients: a meta-analysis.International journal of clinical oncology · 2017Pooled it
- Relationship between LINE-1 hypomethylation and Helicobacter pylori infection in gastric mucosae.Medical oncology (Northwood, London, England) · 2015Trial
- Predictive and prognostic roles of BRAF mutation in stage III colon cancer: results from intergroup trial CALGB 89803.Clinical cancer research : an official journal of the American Association for Cancer Research · 2012Trial
- Global DNA hypomethylation (LINE-1) in the normal colon and lifestyle characteristics and dietary and genetic factors.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2009Trial
- Tumor Vascular Features and Colorectal Cancer-Specific Mortality.JAMA network open · 2026Article
- Article
- Cigarette smoking and long-term incidence of colorectal cancer subclassified by tumor-infiltrating myeloid cells: A prospective cohort study.Environmental pollution (Barking, Essex : 1987) · 2026Article
- Tumor vessel phenotype in colorectal cancer microenvironment according to age at diagnosis.British journal of cancer · 2026Article
- Cytotoxic T-cell exhaustion analyses by in situ single-cell immunofluorescence in relation to colorectal cancer patient age, tissue bacteria and mortality.BMJ oncology · 2026Article
- DNA methylation in adaptation to high-altitude environments and pathogenesis of related diseases.Human genomics · 2025Review
- Exploring transposable elements: new horizons in cancer diagnostics and therapeutics.Mobile DNA · 2025Review
- Simulation-guided pan-cancer analysis identifies a novel regulator of CpG island hypermethylation heterogeneity.Briefings in bioinformatics · 2025Article
- LINE-1 hypomethylation characterizes the inflammatory response in coeliac disease associated-intestinal mucosa and small bowel adenocarcinomas.The Journal of pathology · 2025Article
- Clinicopathological, molecular, and prognostic features of colorectal carcinomas with KRAS c.34G>T (p.G12C) mutation.Cancer science · 2024Article
- Immune microenvironmental heterogeneity according to tumor DNA methylation phenotypes in microsatellite instability-high colorectal cancers.Cancer immunology, immunotherapy : CII · 2024Article
- Unmasking early colorectal cancer clues: in silico and in vitro investigation of downregulated IGF2, SOCS1, MLH1, and CACNA1G in SSA polyps.Molecular biology reports · 2024Article
- Pathogenesis and biomarkers of colorectal cancer by epigenetic alteration.Intestinal research · 2024Review
- Multi-omics cluster defines the subtypes of CRC with distinct prognosis and tumor microenvironment.European journal of medical research · 2024Article
- LINE-1 hypomethylation, increased retrotransposition and tumor-specific insertion in upper gastrointestinal cancer.Cancer science · 2024Article
107 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The CpG island methylator phenotype (CIMP) with widespread promoter CpG island methylation is a phenotype in colorectal cancer, associated with microsatellite instability (MSI) and BRAF mutation. Genome-wide hypomethylation may also play an important role in genomic instability. However, the relation between global DNA methylation level and methylation in individual CpG islands remains uncertain. Utilizing 869 population-based colorectal cancers, we measured long interspersed nucleotide element-1 (LINE-1) methylation level by Pyrosequencing, which correlates with global DNA methylation level. We quantified DNA methylation in 8 CIMP-specific promoters (CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1) by real-time PCR (MethyLight technology). LINE-1 methylation levels in tumors were approximately normally distributed (mean, 61.4%; median, 62.3%; standard deviation, 9.6%). Among the 869 tumors, 128 (15%) were classified as CIMP-high (>or=6/8 methylated promoters). The mean LINE-1 methylation level was higher in CIMP-high tumors (65.1%, p < 0.0001) than non-CIMP-high tumors (60.7%), and higher in MSI-high tumors (64.7%, p < 0.0001) than non-MSI-high tumors (60.7%). When tumors were stratified by MSI/CIMP status, compared to non-MSI-high non-CIMP-high tumors (mean LINE-1 methylation level, 60.4%), the mean LINE-1 methylation level was higher in MSI-high CIMP-high (64.8%, p < 0.0001), MSI-high non-CIMP-high (64.6%, p = 0.03) and non-MSI-high CIMP-high tumors (66.1%, p = 0.0003). In addition, 18q loss of heterozygosity in non-MSI-high tumors was correlated with LINE-1 hypomethylation (p = 0.004). In conclusion, both CIMP-high and MSI-high are inversely associated with LINE-1 hypomethylation, suggesting that CIMP/MSI and genomic hypomethylation may represent different pathways to colorectal cancer. Our data also support a possible link between global hypomethylation and chromosomal instability.
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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.