Thyroid cancer is the most common type of endocrine
malignancy and the incidence is rapidly increasing. Follicular (
FTC) and papillary thyroid (PTC)
carcinomas comprise the well-differentiated subtype and they are the two most common
thyroid carcinomas. Multiple molecular genetic and epigenetic alterations have been identified in various types of thyroid
tumors over the years. Point mutations in BRAF, RAS as well as RET/PTC and PAX8/PPARγ chromosomal rearrangements are common.
Thyroid cancer, including both
FTC and PTC, has been observed in patients with
Carney Complex (CNC), a syndrome that is inherited in an autosomal dominant manner and predisposes to various
tumors. CNC is caused by inactivating mutations in the tumor-suppressor gene encoding the
cyclic AMP (
cAMP)-dependent protein kinase A (PKA) type 1α regulatory subunit (PRKAR1A) mapped in chromosome 17 (17q22-24). Growth of the thyroid is driven by the TSH/cAMP/PKA signaling pathway and it has been shown in mouse models that PKA activation through genetic ablation of the regulatory subunit Prkar1a can cause
FTC. In this review, we provide an overview of the molecular mechanisms contributing to thyroid
tumorigenesis associated with inactivation of the RRKAR1A gene.