The expression of the following oncogene is associated with a high incidence of Medullary carcinoma of thyroid -

RET protooncogene is a growth factor receptor (receptor tyrosine kinase) The RET protein is a receptor for the glial cell lined derived neurotrophic factor and structurally related proteins that promote cell survival during neural development. RET is normally expressed in the following cells Parafollicular C cells of the thyroid Adrenal medulla Parathyroid cell precursors. Point mutation in the RET protooncogenes are associated with the following disorders.  (i) MEN type 2A - There is point mutation in RET extracellular domain which causes constitutive dimerization and activation leading to:- Medullary thyroid carcinoma Adrenal and parathyroid tumours (ii) MEN type 2B - Point mutation in the RET cytoplasmic catalytic domain alter the substrate specificity of the tyrosine kinase and leads to:- Thyroid tumours Adrenal tumors (iii) Sporadic Medullary thyroid carcinoma Somatic rearrangement of the RET gene (iv) Hirschsprung disease This is caused by complete loss of RET function.