The defects in the RET proto-oncogene are the cause of several clinically distinct disorders. The activating (gain-of-function) mutations induce both the familial forms of medullary thyroid carcinoma (MTC), MEN 2 syndromes associated with pheochromocytoma, hyperparathyroidism (MEN 2A) or marfanoid habitus and other lesions (MEN 2B), and sporadic forms of MTC, where the mutations are present only in the tumor tissue. The detection of mutations has considerable diagnostic importance especially for persons at risk when early therapeutical intervention could prevent the onset of the disease. The frequent case of papillary thyroid cancer is the translocation or inversion within theRETproto-oncogene and its fusion with other genes rising in chimeric proteins which activate the RET signalling. Conversely the inactivating (loss-of-function) mutations, deletions or insertions are the most frequent cause of Hirschsprung’s disease marked by lack of innervation of variable lengths of the hind gut. The intensive study of the physiological role of RET protein - the receptor tyrosine kinase - in normal cell proliferation, differentiation and survival promises possible therapeutic application of this knowledge, esp. in the treatment of neurodegenerative disorders.

        Key words: RET proto-oncogene, medullary thyroid carcinoma, papillary carcinoma, MEN 2A, MEN 2B, Hirschsprung’s disease, genetics