Ret oncogene

The RET oncogene (RET = acronym for "rearranged during transfection") codes for a receptor tyrosine kinase that is normally involved in developmental processes. Oncogenic mutations lead to the constitutive activation of the tyrosine kinase. This mechanism is of crucial importance for the development of tumours.

In MEN type 2A syndrome (see Sipple syndrome below), ligand-independent, constitutive activation of the receptor occurs either through various mutations in the cysteine-rich extracellular domain (type 2A, FMTC) or through mutation of codon 918 in the intracellular kinase domain (type 2B). This pathomechanism of the misregulation of the RET receptor by mutation of an allele in the sense of oncogene activation differs from other forms of hereditary tumor disposition, in which there is a loss of function of a protein encoded by a tumor suppressor gene. RET mutations that lead to a loss of function of this receptor cause a completely different clinical picture, namely an autosomal dominant inherited form of megacolon congenitum (Hirschsprung's disease). Approximately 70% of carriers of MEN type 2 develop clinically manifest thyroid carcinoma in the course of their lives, mostly in the second decade of life.

It is remarkable that patients with MEN type 2A are more likely to suffer from Lichen amyloidosus.