Glial cell line-derived neurotrophic factor (GDNF), the most potent trophic factor yet described for both dopaminergic neurons of the substantia nigra and spinal motorneurons, has recently been shown to signal through a multireceptor complex composed of a novel glycosylphosphatidylinositol-anchored GDNF receptor-a (GDNFR-a) and the receptor tyrosine kinase product of the c-ret proto-oncogene (R...

BACKGROUND The RET proto-oncogene encodes a receptor tyrosine kinase. RET oncogenes arise through sporadic and inherited gene mutations and are involved in the etiopathogenesis of medullary thyroid carcinoma, a cancer that responds poorly to conventional chemotherapy. Medullary thyroid carcinoma is a component of multiple endocrine neoplasia type 2 or MEN2 syndromes. METHODS We investigated t...

Multiple Neuroendocrine Neoplasia (MEN) gained notoriety after its initial descriptions, but cases of MEN are extremely rare, especially type 2B, characterized by a clinical presentation involving Medullary Thyroid Carcinoma (MTC), pheochromocytoma, and mutagenic alterations with focus on the RET proto-oncogene. Surgical intervention stands out as primary curative treatment, in metastatic condi...

BACKGROUND Papillary thyroid carcinoma (PTC), which may be sporadic (95%) or familial (5%), has a prevalence adjusted for age in the general population of 1:100 000. Somatic rearrangements of the RET proto-oncogene are present in up to 66% of sporadic tumours, while they are rarely found in familial cases. PURPOSE In order to determine if some variants of this gene, or a combination of them, ...

Germ line missense mutations in the RET proto-oncogene are responsible for the inherited cancer syndrome multiple endocrine neoplasia type 2A (MEN2A). The clinical presentation of the disease and the age at onset varies even within families, where patients carry the same mutation. These variations in phenotypes suggest a role for genetic modifiers, and recently, it has been reported that polymo...

The object of this work was to compare the frequency of three polymorphic changes in the RET proto-oncogene: L769L, S836S, and S904S in patients with medullary thyroid carcinoma (MTC; n = 246) and in the general population (n = 420 for single-nucleotide polymorphism [SNP] L769L and S904S; n = 411 for SNP 836). We tried to investigate how the harbored SNPs affect the age at onset of sporadic med...

OBJECTIVE Restriction analysis is a straightforward procedure for mutational analysis. It is commonly used for screening RET mutations. Incomplete digestion is a well-known cause of false results. Herein, we report another limitation of the method. DESIGN AND METHODS Screening for somatic mutations in RET exons 16, 13 and 15 was performed in a patient with a sporadic medullary thyroid carcino...

We demonstrate that a Hirschsprung (HSCR) mutation in the tyrosine kinase domain of the RET proto-oncogene abolishes in cis the tyrosine-phosphorylation associated with the activating mutation in multiple endocrine neoplasia type 2A (MEN2A) in transiently transfected Cos cells. Yet the double mutant RET2AHS retains the ability to form stable dimers, thus dissociating the dimerization from the p...

Mutations in the rei proto-oncogene constitute the germ line defect in patients with inherited forms of medullary thyroid carcinoma (MTC) and are also present in tumor DNA from a subset of patients with sporadic forms of MTC. We now show that the TT cell line of human MTC can be induced within 48 h to resemble mature C cell differentiation by activation of the nil'-1 signal transduction pathway...

INTRODUCTION The multiple endocrine neoplasia type 2A (MEN 2A) syndrome, comprising medullary thyroid carcinoma (MTC), pheochromocytoma and primary hyperparathyroidism (PHPT) is most frequently caused by codon 634 activating mutations of the RET (rearranged during transfection) proto-oncogene on chromosome 10. For this codon-mutation carriers, earlier thyroidectomy (before the age of 5 years) w...