Epigenetic Dysregulation in Thyroid Neoplasia

Gain-of-function mutations in oncogenes have aided our understanding of the molecular mechanisms of thyroid carcinogenesis. Mutations or deletions cause inactivation of tumor suppressor genes in thyroid carcinomas. However, recent advances have disclosed the significance of epigenetic events in the development and progression of human tumorigenesis. Indeed, various tumor-suppressor genes and thyroid hormone–related genes are epigenetically silenced in thyroid tumors. This article reviews the evidence for epigenetic gene dysregulation in follicular cell–derived thyroid carcinomas including papillary thyroid carcinoma, follicular thyroid carcinoma, and undifferentiated thyroid carcinoma. The authors also discuss future applications of epigenetics as ancillary diagnostic tools and in the design of targeted therapies for thyroid cancer.