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Promoter Methylation of Four Tumor Suppressor Genes in Human Papillary Thyroid Carcinoma
Fatemeh Khatami1, Bagher Larijani2, Ramin Heshmat1
1Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
Background & Objective:
Papillary thyroid cancer (PTC) is considered to be the most common type of thyroid malignancies. Epigenetic alteration, in which the chromatin conformation and gene expression change without changing the sequence of DNA, can occur in some tumor suppressor genes and oncogenes. Methylation is the most common type of epigenetic alterations that can be an excellent indicator of PTC invasive behavior.
Methods:
In this research, we determined the promoter methylation status of four tumor suppressor genes (SLC5A8, RASSF1, MGMT, and DNMT1) and compared the results of 55 PTC cases with 40 goiter patients. For methylation, we used the methylation-sensitive high resolution melting (MS-HRM) assay technique. The resulting graphs of each run were compared with those of 0%, 50%, and 100% methylated controls.
Results:
Our data showed that the promoter methylation of SLC5A8, Ras association domain family member 1(RASSF1), and MGMT were significantly different between PTC tissue and goiter with P-value less than 0.05. The most significant differences were observed in RASSF1; 77.2% of hyper-methylated PTC patients versus 15.6% hyper-methylated goiter samples (P<0.001).
Conclusion:
RASSF1 promoter methylation can be a PTC genetic marker. RASSF1 promoter methylation is under the impact of the methyltransferase genes (DNMT1 and MGMT), protein expression, and promoter methylation.
Insights
Promoter methylation of RASSF1, SLC5A8, and MGMT genes significantly differs between papillary thyroid cancer (PTC) and goiter tissues. RASSF1 promoter methylation shows potential as a diagnostic marker for PTC.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Papillary thyroid cancer (PTC) is the most prevalent thyroid malignancy.
- Epigenetic alterations, specifically DNA methylation, can influence tumor suppressor genes and oncogenes in PTC.
- Methylation patterns serve as potential indicators of PTC's invasive characteristics.
Purpose of the Study:
- To investigate the promoter methylation status of four tumor suppressor genes (SLC5A8, RASSF1, MGMT, DNMT1) in PTC.
- To compare methylation profiles between PTC tissues and non-cancerous goiter tissues.
- To evaluate the potential of RASSF1 promoter methylation as a diagnostic marker for PTC.
Main Methods:
- Utilized methylation-sensitive high-resolution melting (MS-HRM) assay to analyze promoter methylation.
- Examined 55 PTC cases and 40 goiter samples.
- Compared methylation data against standardized controls (0%, 50%, 100%).
Main Results:
- Significant differences in promoter methylation were found for SLC5A8, RASSF1, and MGMT between PTC and goiter tissues (P < 0.05).
- RASSF1 exhibited the most pronounced difference, with 77.2% hyper-methylation in PTC versus 15.6% in goiter (P < 0.001).
- DNMT1 methylation status did not show significant differences between the groups.
Conclusions:
- RASSF1 promoter methylation is a significant distinguishing factor between PTC and goiter.
- RASSF1 promoter methylation can serve as a potential genetic marker for diagnosing PTC.
- RASSF1 methylation is influenced by methyltransferase genes (DNMT1, MGMT) and their expression levels.
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