The RET tyrosine kinase is a functional receptor for neurotrophic ligands of the glial cell line-derived neurotrophic factor (GDNF) family. Loss of function of RET is associated with congenital megacolon or Hirschsprung's disease, whereas germ-line point mutations causing RET activation are responsible for multiple endocrine neoplasia type 2 (MEN2A, MEN2B, and familial medullary thyroid carcino...

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant disorder that can be distinguished as three different syndromes: multiple endocrine neoplasia type 2A (MEN2A), MEN2B and familial medullary thyroid carcinoma (FMTC). This disorder is usually caused by the mutations of the rearranged during transfection protooncogene gene (RET) or the neurotrophic tyrosine kinase receptor type 1...

Mutations of the Ret receptor tyrosine kinase are responsible for inheritance of multiple endocrine neoplasia (MEN2A and MEN2B) and familial medullary thyroid carcinoma syndromes. Although several familial medullary thyroid carcinoma and most MEN2A mutations involve substitutions of extracellular cysteine residues, in most MEN2B cases there is a methionine-to-threonine substitution at position ...

BACKGROUND Germline mutations of the RET proto-oncogene identical to those found in the tumour predisposition syndrome multiple endocrine neoplasia type 2A (MEN2A), were detected in 2.5-5% of sporadic and familial cases of Hirschsprung's disease. Some patients with Hirschsprung's disease may therefore be exposed to a highly increased risk of tumours. AIMS To define clinical use of RET gene te...

Multiple endocrine neoplasia type 2A (MEN2A) is an autosomal dominant inherited condition that predisposes to the triad of medullary thyroid cancer (MTC), pheochromocytoma (Pheo), and primary hyperparathyroidism (PHT). Nearly 100% of MEN2A are associated with germ line mutation of the RET proto-oncogene (RET), and DNA-based RET genotype analysis is now considered essential for earlier diagnosis...

Multiple endocrine neoplasia type 2A (MEN2A) is a rare syndrome caused almost by germline RET mutation, and characterized medullary thyroid carcinoma (MTC), in combination or not with pheochromocytoma (PHEO), hyperparathyroidism (HPTH), cutaneous lichen amyloidosis (CLA), Hirschsprung's disease (HD). The basal serum calcitonin (Ctn)/carcinoembryonic antigen (CEA) levels are significantly correl...

The c-RET proto-oncogene encodes a receptor-type tyrosine kinase, and its mutations in the germ line are responsible for the inheritance of multiple endocrine neoplasia type 2A (MEN2A) and 2B (MEN2B). Ret kinases are constitutively activated as a result of MEN2A mutations (Ret-MEN2A) or MEN2B mutations (Ret-MEN2B). Here we demonstrate that UV light (UV) irradiation induces superactivation of th...

Hereditary medullary thyroid carcinoma (MTC) presents within the context of 3 genetic syndromes. Multiple endocrine neoplasia type 2A (MEN2A, Sipple’s syndrome) is an autosomal-dominant genetic syndrome that includes MTC, pheochromocytoma, and primary hyperparathyroidism (PHPT). MEN2B is an autosomal-dominant genetic syndrome that includes MTC, pheochromocytoma, multiple mucosal neuromas, and a...

An oncogenic mutant of c-RET as a receptor-type tyrosine kinase, termed RET-MEN2A, displays both cell-transforming activity in vivo and strong catalytic activity in vitro. In this study, we compared the activities of mutant RET-MEN2A with substitutions of each of nine tyrosines for phenylalanine (Y1062F, Y1015F, Y981F, Y952F, Y928F, Y905F, Y900F, Y864F, and Y826F), which had been transfected in...

The multiple endocrine neoplasia type 2A (MEN2A) is a monogenic disorder characterized by an autosomal dominant pattern of inheritance which is characterized by high risk of medullary thyroid carcinoma in all mutation carriers. Although this disorder is classified as a rare disease, the patients affected have a low life quality and a very expensive and continuous treatment. At present, MEN2A is...