Molecular Biology of Thyroid Cancer

Our medical discoveries often follow advancement in biologic techniques. The use of karyotypic analysis, fluorescent in situ hybridization, candidate gene sequencing, microarray expression analysis, and whole-genome associations has helped determine the molecular defects causing thyroid cancer. These and future discovered defects will allow clear classifications, precise prognosis, and targeted therapy. Genetic events involved in the development of well-differentiated papillary thyroid carcinoma (PTC) include rearrangement of the tyrosine receptor kinase RET and TRK and activating mutations of the intracellular signaling effectors BRAF (B-type Raf kinase) and RAS (see Fig. 2.1) [1]. Rearrange ment of PAX8/PPARg (peroxisome proliferator–activated receptor) and RAS mutations are frequent in well-differentiated follicular thyroid carcinoma (FTC). These mutations occasionally have been identified in benign follicular adenoma (FA). Also, loss of phosphate and tensin homolog (PTEN) and activation of PI3K/ AKT are involved in FTC pathogenesis. Progression of PTC and FTC to anaplastic thyroid carcinoma (ATC) is associated with mutation of p53, b catenin, as well as members of PI3K/AKT pathway. Recent reports suggest that additional molecular mechanisms such as epigenetic modification and microRNA deregulation are involved in the development of thyroid tumorigenesis. This review summarizes the molecular characterization of thyroid cancer and the molecular mechanisms involved in thyroid carcinogenesis. Table 2.1 lists the nomenclature for the various abbreviations used throughout the text.