The fundamental role of epigenetic events in cancer
Abstract
Patterns of DNA methylation and chromatin structure are profoundly altered in neoplasia and include genome-wide losses of, and regional gains in, DNA methylation. The recent explosion in our knowledge of how chromatin organization modulates gene transcription has further highlighted the importance of epigenetic mechanisms in the initiation and progression of human cancer. These epigenetic changes -- in particular, aberrant promoter hypermethylation that is associated with inappropriate gene silencing -- affect virtually every step in tumour progression. In this review, we discuss these epigenetic events and the molecular alterations that might cause them and/or underlie altered gene expression in cancer.
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Promoter-CGI methylation is associated with gene silencing.
“promoter-CGI methylation is associated with gene silencing [26, 43].”
DNA methylation is an essential epigenetic mechanism influencing chromatin structure, regulation of transcription and genome stability.
“DNA methylation, which consists on the addition of a methyl group at carbon 5 of cytosine in cytosine-guanine dinucleotides (CpG), is an essential epigenetic mechanism influencing chromatin structure, regulation of transcription and genome stability [26, 43].”
Hypermethylation across multiple tumor types occurs predominantly in genes that are specifically repressed in the tissue of origin.
“our results support that hypermethylation across multiple tumor types occurs predominantly in genes that are specifically repressed in the tissue of origin”
During carcinogenesis, global hypomethylation of DNA occurs in parallel with hypermethylation of CGIs in the promoter regions.
“It has been widely described that during the process of carcinogenesis a global hypomethylation of DNA occurs in parallel with the hypermethylation of CGIs in the promoter regions [26, 43].”
DNA methylation is a key epigenetic modification that regulates gene expression and plays an essential role in cancer development.
“DNA methylation is a key epigenetic modification that regulates gene expression and plays an essential role in cancer development [17, 26].”
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- Authors
- Jones, P. A., & Baylin, S. B.
- Affiliations
- University of Southern California (US)
- Johns Hopkins University (US)
- Corresponding author
- Jones, Peter A.
- Baylin, Stephen B.
- Venue
- Nature Reviews Genetics
- Published
- 2002-06
- Volume
- 3
- Issue
- 6
- Pages
- 415-428
- ISSN
- 1471-0056 (ISSN-L)
- 1471-0064
- OpenAlex
- W1504303645
- Cited by
- 5,648
- References
- 7
- Citations by year
- 2026: 62 · 2025: 99 · 2024: 129 · 2023: 176 · 2022: 119 · 2021: 214 · 2020: 161 · 2019: 178 · 2018: 169 · 2017: 230 · 2016: 215 · 2015: 262 · 2014: 287 · 2013: 298 · 2012: 345
- FWCI
- 16.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute
- National Institute of Environmental Health Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- epigenetics, cancer, DNA methylation, chromatin structure, promoter hypermethylation, gene silencing, tumor progression, gene expression regulation, chromatin organization
- MeSH terms
- Chromosome Mapping, Humans, Mass Screening, Neoplasms, Signal Transduction, Genome, Human, DNA Methylation
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