Promoter Methylation of Four Tumor Suppressor Genes in Human Papillary Thyroid Carcinoma

Abstract

<span style="font-size: 14px;"><span style="text-align: justify;"><span style="font-family: 'times new roman';"><strong><span style="color: #0000ff;">Background & Objective:</span></strong></span></span></span><br /> <span style="font-size: 14px;"><span style="font-family: times new roman;">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.</span></span><br /> <span style="font-size: 14px;"><span style="text-align: justify;"><span style="font-family: 'times new roman';"><span style="color: #0000ff;"><strong>Methods:</strong></span></span></span></span><br /> <span style="font-size: 14px;"><span style="font-family: times new roman;">In this research, we determined the promoter methylation status of four tumor suppressor genes (<em>SLC5A8, RASSF1, MGMT, </em>and<em> DNMT1)</em> 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.</span></span><br /> <span style="font-size: 14px;"><span style="text-align: justify;"><span style="font-family: 'times new roman';"><strong><span style="color: #0000ff;">Result:</span></strong></span></span></span><br /> <span style="font-size: 14px;"><span style="font-family: times new roman;">Our data showed that the promoter methylation of <em>SLC5A8</em>, <em>Ras association domain family member 1(RASSF1)</em>, and <em>MGMT</em> were significantly different between PTC tissue and goiter with P-value less than 0.05. The most significant differences were observed in <em>RASSF1</em>; 77.2% of hyper-methylated PTC patients versus 15.6% hyper-methylated goiter samples (<em>P</em><0.001).</span></span><br /> <span style="font-size: 14px;"><span style="text-align: justify;"><span style="font-family: 'times new roman';"><strong><span style="color: #0000ff;">Conclusion:</span></strong></span></span></span><br /> <span style="font-size: 14px;"><span style="font-family: times new roman;"><em>RASSF1</em> promoter methylation can be a PTC genetic marker. <em>RASSF1</em> promoter methylation is under the impact of the methyltransferase genes (<em>DNMT1</em> and <em>MGMT</em>), protein expression, and promoter methylation.</span></span>