ABSTRACT
Thyroid cancer is the most common endocrine malignancy, and its incidence has increased over the past three decades. Thyroid cancers arise from the thyroid follicular cell or parafollicular C cells. Papillary thyroid carcinomas are driven by the MAPK pathway, with the two main driver mutations being BRAF and RAS. The RET gene oncogenic gene translocation is another driver for papillary thyroid carcinoma tumorigenesis. Follicular thyroid carcinoma is primarily driven by the RAS mutations, which include the PI3K-AKT and the RASSF1-MST1-FOXO3 signaling pathway, as well as the PAX8/PPARG gene fusion. The Cancer Genome Atlas analysis of the genomic alterations seen in poor and anaplastic thyroid carcinomas support a stepwise progression and dedifferentiation from well-differentiated thyroid carcinomas to eventually poorly differentiated thyroid carcinomas and finally anaplastic thyroid carcinomas, with increasing mutation burden as it becomes more dedifferentiated. The main driver for medullary thyroid carcinomas is the RET gene, in both sporadic and hereditary cases. The genomic landscaping of thyroid cancers with the use of next-generation sequencing methods have allowed for a better understanding of the various driver mutations in the stepwise carcinogenesis pathway of various thyroid carcinomas. Such molecular mapping of the pathogenesis of thyroid carcinomas could hopefully in the future allow for precision-based medicine personalized therapy based on tumor molecular signatures of an individual.
