Rearranged during transfection–papillary thyroid carcinoma fusion protein (RET/PTC)

**RET/PTC** refers to a family of **chimeric oncogenic fusion proteins** arising from chromosomal rearrangements involving the **RET (rearranged during transfection) proto-oncogene** and various partner genes, most commonly **CCDC6 (RET/PTC1)** and **NCOA4 (RET/PTC3)**. These rearrangements are characterized by the fusion of the 5' region of a partner gene with the 3' region of **RET** encoding its intracellular kinase domain, resulting in constitutive ligand-independent activation of the RET kinase. This activation triggers downstream signaling cascades, mainly the **RAS/RAF/MEK/ERK (MAPK)** and **PI3K/AKT** pathways, which drive uncontrolled cell proliferation, survival, and differentiation. RET/PTC fusions are a defining molecular feature of **papillary thyroid carcinoma (PTC)**, especially in cases following radiation exposure and in pediatric patients. Multiple drugs target RET/PTC-driven cancers, primarily through kinase inhibition. RET/PTC rearrangements serve as diagnostic biomarkers and potential targets for personalized therapy[2][3][4][5][6][8][9][10]. RET/PTC is not a single unique protein but a class of oncogenic RET fusions—hence structured drug and biomarker data should be linked to specific RET fusion partners when possible. RET/PTC proteins are therapeutically actionable molecular targets in thyroid cancer and are relevant for molecular diagnostics, targeted therapy, and as a model for fusion-driven oncogenesis.

Other names

RET/PTC fusion proteinRET::PTCRET/PTC1, RET/PTC3 (individual fusion types)CCDC6-RET, NCOA4-RET (common partner gene fusions)RET fusion protein

Inhibition of the RET tyrosine kinase domain blocks constitutive downstream signaling pathways (MAPK, PI3K/AKT), halting proliferation and tumor growth Prevention of ligand-independent dimerization and autophosphorylation