J Korean Thyroid Assoc.  2014 Nov;7(2):118-128. 10.11106/cet.2014.7.2.118.

Gene Methylation Associated with Differentiated Thyroid Cancer

• Tae SY
• Chi HK
• Kim SJ
• Lee KE
• Youn YK

• KMID: 2095122
• DOI: http://doi.org/10.11106/cet.2014.7.2.118

Abstract

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.

Keyword

Epigenetics; Methylation; Thyroid cancer; Genes; Tumor suppressor

MeSH Terms

Base Sequence
Carcinogenesis
Epigenomics
Genes, Tumor Suppressor
Ion Transport
Methylation*
Prognosis
Promoter Regions, Genetic
Thyroid Neoplasms*
Thyrotropin
Thyrotropin

Figure

• 

  Fig. 1. CpG island methylation. (A) In a normal cell, CpG islands have no methylated cytosine residue and allow transcriptional activity. (B) DNA methylation at the 5 position of cytosine has the specific effect of reducing gene expression by gene silencing. Methylated CpG islands contribute to loss of gene function.

• 

  Fig. 2. Thyroidal iodide-metabolizing molecules. A unique physiological function of thyroid gland is ability to uptake, concentrate and use iodide to synthesize thyroid hormones. This process involves several key protein molecules that are specifically expressed in follicular epithelial cells of the thyroid gland. Thyroid stimulating hormone receptor (TSHR) bound to TSH stimulates iodide transport into the thyroid gland by the sodium iodide symporter (NIS). The function of pendrin is to transport iodide into the follicular lumen from the thyroid cell. The genes of thyroid specific molecules (red arrow) are methylated in the promoter areas in thyroid tumors.

Reference

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