The RET oncogene in papillary thyroid carcinoma

Abstract

Papillary thyroid carcinoma (PTC) is the most common form of thyroid cancer, accounting for greater than 80% of cases. Surgical resection, with or without postoperative radioiodine therapy, remains the standard of care for patients with PTC, and the prognosis is generally excellent with appropriate treatment. Despite this, significant numbers of patients will not respond to maximal surgical and medical therapy and ultimately will die from the disease. This mortality reflects an incomplete understanding of the oncogenic mechanisms that initiate, drive, and promote PTC. Nonetheless, significant insights into the pathologic subcellular events underlying PTC have been discovered over the last 2 decades, and this remains an area of significant research interest. Chromosomal rearrangements resulting in the expression of fusion proteins that involve the rearranged during transfection (RET) proto-oncogene were the first oncogenic events to be identified in PTC. Members of this fusion protein family (the RET/PTC family) appear to play an oncogenic role in approximately 20% of PTCs. Herein, the authors review the current understanding of the clinicopathologic role of RET/PTC fusion proteins in PTC development and progression and the molecular mechanisms by which RET/PTCs exert their oncogenic effects on the thyroid epithelium. Thyroid malignancy is 2.5-fold more common in women than in men; and, between 1993 and 2001, the age-adjusted incidence of thyroid malignancy in American women increased at a rate of 4.3% per year: more rapidly than any other cancer subtype monitored by the Surveillance, Epidemiology, and End Results (SEER) database.

ALK,ROS1 and NTRK3 gene rearrangements in inflammatory myofibroblastic tumours

“…Rearrangements of other RTKs have also been reported in minor subsets of IMT. The RET fusion gene is well known in papillary thyroid carcinoma . Antonescu et al .…”

“…The RET fusion gene is well known in papillary thyroid carcinoma. 37 Antonescu et al reported the presence of RET rearrangement in only one of 62 IMTs, although no fusion partner gene has been discovered to date. 21 In the current study, we failed to find RET rearrangement by FISH, suggesting that such a rearrangement may be an extremely rare event in IMT.…”

Tall cell variant of papillary thyroid carcinoma: current evidence on clinicopathologic features and molecular biology

“…Up to now, 13 different RET/PTC oncogenes have been discovered, and RET/PTC1 and RET/PTC3 represent the most common types, accounting for approximately 90% of RET-associated PTC [51, 52]. Only one study compared the occurrence of RET/PTC between TCV and cPTC in literature.…”

Molecular Markers and Thyroid Cancer.

“…RET binds the family of GDNF (glial neuron derived factor) neurotrophic growth factors. In normal conditions, binding of the ligand to the extracellular portion of the receptor allows dimerization of the receptor, phosphorylation in tyrosine kinase cytoplasmic domain and consequent activation of the MAPK signaling pathway (Prescott, 2015).…”