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DNA Methylation in Solid Tumors: Functions and Methods of Detection
Andrea Martisova1, Jitka Holcakova1, Nasim Izadi1
1Masaryk Memorial Cancer Institute, Zluty Kopec 7, 656 53 Brno, Czech Republic.
Abstract:
DNA methylation, i.e., addition of methyl group to 5'-carbon of cytosine residues in CpG dinucleotides, is an important epigenetic modification regulating gene expression, and thus implied in many cellular processes. Deregulation of DNA methylation is strongly associated with onset of various diseases, including cancer. Here, we review how DNA methylation affects carcinogenesis process and give examples of solid tumors where aberrant DNA methylation is often present. We explain principles of methods developed for DNA methylation analysis at both single gene and whole genome level, based on (i) sodium bisulfite conversion, (ii) methylation-sensitive restriction enzymes, and (iii) interactions of 5-methylcytosine (5mC) with methyl-binding proteins or antibodies against 5mC. In addition to standard methods, we describe recent advances in next generation sequencing technologies applied to DNA methylation analysis, as well as in development of biosensors that represent their cheaper and faster alternatives. Most importantly, we highlight not only advantages, but also disadvantages and challenges of each method.
Insights
DNA methylation, an epigenetic process, is crucial for gene regulation and implicated in cancer. This review covers its role in carcinogenesis and methods for its analysis, including new technologies.
Area of Science:
- Epigenetics
- Molecular Biology
- Oncology
Background:
- DNA methylation is a key epigenetic modification regulating gene expression.
- Aberrant DNA methylation is linked to various diseases, particularly cancer.
Purpose of the Study:
- To review the role of DNA methylation in carcinogenesis.
- To discuss methods for DNA methylation analysis in solid tumors.
Main Methods:
- Sodium bisulfite conversion
- Methylation-sensitive restriction enzymes
- Methyl-binding proteins/antibodies against 5-methylcytosine (5mC)
- Next-generation sequencing
- Biosensors
Main Results:
- DNA methylation dysregulation is prevalent in solid tumors.
- Various analytical methods exist, each with pros and cons.
- Next-generation sequencing and biosensors offer advanced alternatives.
Conclusions:
- Understanding DNA methylation's role in cancer is vital.
- Methodological choices impact DNA methylation analysis outcomes.
- Ongoing technological advancements improve detection and analysis.
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