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Hypomethylation of cytosine 5-methyltransferase in human neoplasms
T L Butler1, P H Kay, P F Jacobsen
1Department of Pathology, University of Western Australia, Nedlands, Australia.
Abstract:
Cytosine methylation is an epigenetic modification of DNA involved in control of gene expression. Neoplastic cells exhibit various alterations both in DNA methylation and activity of the enzyme responsible for this modification, 5-methyltransferase (5-MeTase). As there is little requirement for 5-methyltransferase expression in normal cells except during mitosis, we argued that the gene would be hypermethylated in normal cells. Southern analysis revealed almost complete methylation of the gene in genomic DNA from the peripheral blood leukocytes of healthy subjects and a primary fibroblast derived cell line. In contrast, in DNA from a range of tumour tissues and tumour derived cell lines, 5-MeTase exhibited marked hypomethylation. The results of this study indicate that dysregulation of the DNA methylating machinery, especially with respect to the methylation status of 5-MeTase, is a feature of a wide range of neoplasms.
Insights
DNA methylation changes, specifically in 5-methyltransferase (5-MeTase), are altered in cancer. Normal cells show hypermethylation of 5-MeTase, while tumor cells exhibit hypomethylation, indicating dysregulation in neoplastic diseases.
Area of Science:
- Epigenetics
- Molecular Biology
- Cancer Research
Background:
- Cytosine methylation is a key epigenetic mechanism regulating gene expression.
- Neoplastic cells display aberrant DNA methylation patterns and altered 5-methyltransferase (5-MeTase) activity.
- Normal cells have minimal need for 5-MeTase expression outside of mitosis.
Purpose of the Study:
- To investigate the methylation status of the 5-methyltransferase (5-MeTase) gene in normal versus neoplastic cells.
- To determine if dysregulation of 5-MeTase methylation is associated with cancer.
Main Methods:
- Southern blot analysis was used to assess DNA methylation.
- Genomic DNA was analyzed from peripheral blood leukocytes of healthy individuals and a fibroblast cell line.
- DNA from various tumor tissues and tumor-derived cell lines was also analyzed.
Main Results:
- The 5-MeTase gene was found to be almost completely methylated in genomic DNA from normal cells.
- In contrast, a marked hypomethylation of the 5-MeTase gene was observed in DNA from a range of tumor tissues and cell lines.
- These findings suggest a significant difference in 5-MeTase methylation between normal and cancerous cells.
Conclusions:
- Dysregulation of the DNA methylating machinery, particularly the methylation status of 5-MeTase, is a characteristic feature of numerous neoplasms.
- Alterations in 5-MeTase methylation may play a role in the development or progression of cancer.
- This study highlights the importance of epigenetic modifications in cancer biology.