Thyroid carcinoma is the most common malignant endocrine
neoplasia. Differentiated
thyroid carcinomas (DTCs) represent more than 90% of all
thyroid carcinomas and comprise the papillary and
follicular thyroid carcinoma subtypes.
Anaplastic thyroid carcinomas correspond to less than 1% of all thyroid
tumors and can arise de novo or by dedifferentiation of a differentiated
tumor. The etiology of DTCs is not fully understood. Several genetic events have been implicated in thyroid
tumorigenesis. Point mutations in the BRAF or RAS genes or rearranged in transformation (RET)/
papillary thyroid carcinoma (PTC) gene rearrangements are observed in approximately 70% of papillary
cancer cases. Follicular
carcinomas commonly harbor RAS mutations and paired box gene 8 (PAX8)-peroxisome proliferator-activated receptor γ (PPARγ) rearrangements.
Anaplastic carcinomas may have a wide set of genetic alterations, that include gene effectors in the
mitogen-activated protein kinase (MAPK),
phosphatidylinositol 3-kinase (PI3K) and/or β-
catenin signaling pathways. These distinct genetic alterations constitutively activate the MAPK, PI3K and β-
catenin signaling pathways, which have been implicated in
thyroid cancer development and progression. In this context, the evaluation of specific genes, as well as the knowledge of their effects on thyroid
carcinogenesis may provide important information on disease presentation, prognosis and
therapy, through the development of specific
tyrosine kinase targets. In this review, we aimed to present an updated and comprehensive review of the recent advances in the understanding of the genetic basis of follicular cell-derived
thyroid carcinomas, as well as the molecular mechanisms involved in
tumor development and progression.