Gene Methylation Associated with Differentiated Thyroid Cancer / 대한갑상선학회지

Epigenetic alteration changes expression of many genes, such as tumor suppressor gene and molecular specific gene, without change in DNA sequence. Cancers, including thyroid cancer, often exhibit an aberrant methylation of gene promoter regions, which is associated with loss of gene function. Aberrant methylation plays a fundamental role in tumorigenesis. Methylation of some genes tends to occur in certain types of thyroid cancer. Methylation of TIMP3, SLC5A8, p16, RARbeta2, DAPK genes is associated with papillary thyroid cancer. Some studies show that aberrant methylation is related to the BRAF V600E mutation. Methylation of PTEN and RASSF1A genes occurs commonly in follicular thyroid cancer. Methylation of thyroid-specific genes, such as sodium/iodide symporter, thyroid-stimulating hormone receptor, and SLC26A4 which encodes pendrine, also has a relation to thyroid cancer. Methylation of these genes could be utilized as markers to detect early disease, to define prognosis and to predict therapeutic targets of thyroid cancer.

Genetic Alterations in Follicular Cell-derived Thyroid Carcinomas / 대한내분비외과학회지

The molecular approaches to human diseases are receiving greater attention following the completion of the Human Genome Project. Molecular biology techniques are being widely applied to the field of tumor biology, and thyroid carcinomas are not an exception; several genetic alterations have been suggested to play roles in thyroid carcinogenesis and its progression. Malignant tumors arising from thyroid follicular cells can be classified into papillary carcinoma, follicular carcinoma, poorly differentiated carcinoma and anaplastic carcinoma. BRAF mutation, RET/PTC rearrangement and RAS mutation are the suggested molecular causes of papillary thyroid carcinoma (PTC). RAS mutation, PAX8- PPARγ rearrangement, PTEN mutation or methylation, and PIK3CA mutation are known to induce follicular thyroid carcinoma (FTC). Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) are related to adding p53 or β-catenin gene alterations to those of papillary or follicular carcinomas. The more aggressive genetic alterations are added stepwise as thyroid tumors advance from differentiated PTC or FTC to less differentiated PDTC and finally to ATC. Studying the molecular mechanisms underlying thyroid carcinogenesis may help overcome the limitations of the current diagnostic methods and this may provide more accurate diagnostic and prognostic tools. Furthermore, research at the molecular level is essential for personalized therapies and creating targeted therapies for thyroid carcinomas.