Gene methylation in thyroid tumorigenesis.
Aberrant gene methylation plays an important role in human tumorigenesis, including thyroid tumorigenesis. Many tumor suppressor genes are aberrantly methylated in thyroid cancer, and some even in benign thyroid tumors, suggesting a role of this epigenetic event in early thyroid tumorigenesis. Methylation of some of these genes tends to occur in certain types of thyroid cancer and is related to specific signaling pathways. For example, methylation of PTEN and RASSF1A genes occurs mostly in follicular thyroid cancer, and its tumorigenic role may be related to the phosphatidylinositol 3-kinase/Akt signaling pathway, whereas methylation of genes for tissue inhibitor of metalloproteinase-3, SLC5A8, and death-associated protein kinase occurs in papillary thyroid cancer and is related to the BRAF/MAPK kinase/MAPK pathway. Methylation of thyroid-specific genes, such as those for sodium/iodide symporter and thyroid-stimulating hormone receptor, is also common in thyroid cancer. Although its tumorigenic role is not clear, methylation, and hence silencing, of these thyroid-specific genes is a cause for the failure of clinical radioiodine treatment of thyroid cancer. Unlike gene methylation, histone modifications have been relatively poorly investigated in thyroid tumors. Future studies need to emphasize the mechanistic aspects of these two types of epigenetic alterations to uncover new molecular mechanisms in thyroid tumorigenesis and to provide novel therapeutic targets for thyroid cancer.
Xing
Mingzhao
M
Division of Endocrinology and Metabolism, The Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 333, Baltimore, MD 21287, USA. mxing1@jhmi.edu
D000818:Animals; D002291:Carcinoma, Papillary / Q000235:genetics*; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006657:Histones / Q000378:metabolism; D006801:Humans; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics*
D006657:Histones; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf