Reverting the cancer phenotype using the CRISP-R/Cas9 method in an MTC-derived cell line harbor a RET mutation.
Medullary thyroid carcinoma (MTC) arises from parafollicular C cells of the thyroid and accounts from 3 to 5% of all thyroid cancers. MTC is mainly sporadic, but a hereditary pattern is present in 20-30% of cases, transmitted as an autosomal-dominant trait.
The predisposing gene for MTC is localized in the pericentromeric region of chromosome 10, and it is REarranged during Transfection (RET).
Different RET gain-of-function mutations are associated with medullary thyroid cancer (MTC). These mutations lead to constitutive activation and aberrant expression or activation of the receptor.
In particular, studying molecular processes involved in medullary thyroid carcinoma is impossible to perform in physiological conditions. The difficulties are included in the absence of a commercial cell line of normal parafollicular cells.
This project aims to generate a stable line containing parafollicular cells without mutations in RET gene.
We will exploit the new CRISP-R/Cas9 technologies to eliminate the RET mutation harbor by TT cell line. The resulting cell line will be used to study all molecular processes involving RET gene in physiological conditions.