S&S Publications ® page 13 Journal of Basic & Clinical Medicine

The present review summarizes current knowledge on the alterations of molecular genetics and epigenetics of sporadic thyroid follicular cell neoplasms and the relationship of the alterations with multistep carcinogenesis theory. Approximately 50 % of follicular thyroid carcinomas have mutations in RAS family genes or PAX8/PPARγ gene rearrangements. These mutations are found in a mutually exclusive manner, which suggests that follicular thyroid carcinomas develop via two different initiating mechanisms. BRAF gene mutations and RET/PTC and NTRK1 rearrangements that involve the mitogen-activated protein kinase pathway are found in the majority of papillary thyroid carcinoma. These mutations are also found in a mutually exclusive manner and contribute to the initiation of the transformation from normal follicular cells to papillary thyroid carcinoma. TP53 mutations are almost exclusively found in poorly differentiated carcinoma and undifferentiated carcinoma and play an essential role in tumor progression. Aberrant methylation of oncogenes and suppressor oncogenes such as the PTEN gene also causes tumor progression. Growth factors (FGF, FGFR, MET, EGFR and VGEF), cell cycle regulators (cyclin D1, RB, p16, p21 and p27) and adhesion molecules (E-cadherin and fibronectin) activate the mitogenic signaling pathways and have impacts on the initiation, promotion and progression of thyroid carcinomas