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Long interspersed nuclear element-1 hypomethylation in cancer: biology and clinical applications
Open accessAbstract
UNLABELLED: Epigenetic changes in long interspersed nuclear element-1s (LINE-1s or L1s) occur early during the process of carcinogenesis. A lower methylation level (hypomethylation) of LINE-1 is common in most cancers, and the methylation level is further decreased in more advanced cancers. Consequently, several previous studies have suggested the use of LINE-1 hypomethylation levels in cancer screening, risk assessment, tumor staging, and prognostic prediction. Epigenomic changes are complex, and global hypomethylation influences LINE-1s in a generalized fashion. However, the methylation levels of some loci are dependent on their locations. The consequences of LINE-1 hypomethylation are genomic instability and alteration of gene expression. There are several mechanisms that promote both of these consequences in cis. Therefore, the methylation levels of different sets of LINE-1s may represent certain phenotypes. Furthermore, the methylation levels of specific sets of LINE-1s may indicate carcinogenesis-dependent hypomethylation. LINE-1 methylation pattern analysis can classify LINE-1s into one of three classes based on the number of methylated CpG dinucleotides. These classes include hypermethylation, partial methylation, and hypomethylation. The number of partial and hypermethylated loci, but not hypomethylated LINE-1s, is different among normal cell types. Consequently, the number of hypomethylated loci is a more promising marker than methylation level in the detection of cancer DNA. Further genome-wide studies to measure the methylation level of each LINE-1 locus may improve PCR-based methylation analysis to allow for a more specific and sensitive detection of cancer DNA or for an analysis of certain cancer phenotypes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13148-011-0032-8) contains supplementary material, which is available to authorized users.
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“L1s are activated by loss of DNA methylation, which often occurs during premalignant hyperplasia125; the resulting IFN-I response could then trigger cell death pathways.”
From The role of retrotransposable elements in ageing and age-associated diseases (2021) · cites this paper as [125]
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Metadata
- Authors
- Kitkumthorn, N., & Mutirangura, A.
- Affiliations
- Mahidol University (TH)
- Chulalongkorn University (TH)
- Corresponding author
- Mutirangura, Apiwat
- Venue
- Clinical Epigenetics
- Published
- 2011-04-10
- Volume
- 2
- Issue
- 2
- Pages
- 315-330
- ISSN
- 1868-7075 (ISSN-L)
- 1868-7083
- PMC
- PMC3365388
- OpenAlex
- W2052350723
- Cited by
- 142
- References
- 137
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 7 · 2022: 9 · 2021: 7 · 2020: 7 · 2019: 11 · 2018: 15 · 2017: 17 · 2016: 6 · 2015: 15 · 2014: 14 · 2013: 15 · 2012: 8
- FWCI
- 5.07
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Clinical Epigenetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Chulalongkorn University
- Thailand Research Fund
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- LINE-1 hypomethylation, DNA methylation, cancer epigenetics, carcinogenesis, cancer screening, cancer risk assessment, tumor staging, prognostic factors, genomic instability, gene expression changes
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