RET Synthesis

The development of thyroid cancer arises from mutations in either receptor tyrosine kinases or effectors involved in those pathways. In particular, papillary carcinomas generally have alterations in the mitogen-activated protein kinase pathway (MAPK). For example, RET stands for "rearranged during transfection." RET is expressed in high amounts from the C cells in the thyroid, and the RET proto-oncogene is activated by fusion of the RET TK domain with the 5′ sequence of one of different heterologous genes7. These rearrangements generate a series of chimeric-transforming oncogenes collectively described as RET/PTCs, resulting in abnormal proteins constitutively activated from RET kinase7. This occurs independently of the binding to extra-cellular ligands that activate multiple intracellular signaling pathways, thereby leading to clonal expansion and neoplastic transformation of the thyroid follicle cells7. This is known as the RET/PTC rearrangement, and the most common one is RET/PTC1. This is formed by the fusion of RET and the H4 gene. Once this is rearranged, this affects the RET tyrosine kinase receptor. The …show more content…
BRAF is an effector of the Mapk signaling cascade, and incurs a point mutation on nucleotide 1799, which results in a valine to glutamate substitution at residue 600. This mutated form of the BRAF gene has been found to disrupt the hydrophobic interactions in between the activation loop and the ATP binding site, which results in a constitutive expression of MEK, and ultimately transcription factors that perpetuate cellular differentiation, cellular proliferation, and cellular survival7. Research has determined that these mutations involving either the RET/PTC and BRAF mutation do not generally overlap, and that a functional BRAF gene is needed to see the oncogenic effects of the RET/PTC