The RAS-RAF-MEK-ERK-MAP kinase pathway mediates the cellular response to extracellular signals that regulate cell proliferation, differentiation, and apoptosis. Mutation of the RAS proto-oncogene occurs in various thyroid neoplasms such as papillary thyroid carcinomas (PTCs), follicular thyroid adenomas and carcinomas. A second genetic alteration frequently involved in PTC is RET/PTC rearrangem...

Medullary thyroid carcinoma (MTC) is an uncommon malignancy of hereditary and sporadic presentation. Mutations in the RET proto-oncogene are involved in the pathogenesis of familial MTC and >50% of the sporadic cases. Currently, there is no effective treatment for recurrent or metastatic MTC. We report here a rapid response to a sorafenib (RET and RAF kinase and vascular endothelial growth fact...

approximately 5-10% of all thyroid cancers are medullary thyroid carcinomas (mtc). mtc is mainly sporadic in nature, but 20-30% of cases are hereditary. genetic testing for hereditary mtc is very important for the patient and his family, but the patients must be receiving appropriate genetic counseling. about 98% of patients with hereditary mtc have germline mutations in exons 10, 11, 13, 14, 1...

Hirschsprung disease (HSCR) is a common genetic disorder presenting with functional intestinal obstruction secondary to enteric aganglionosis. HSCR can be familial or sporadic. Although five putative susceptibility genes have been identified, only germline mutations in the RET proto-oncogene account for a significant minority (up to 50%) of familial HSCR; 3% of sporadic HSCR in a population bas...

BACKGROUND Multiple endocrine neoplasia type 2A (MEN 2A) is an autosomal dominant inherited cancer syndrome that affects multiple tissues derived from the neural crest. Inheritance of MTC is related to the presence of specific mutations in the RET proto-oncogene. Almost all mutations in MEN 2A involve one of the cysteines in the extracellular domain of the RET receptor. AIMS The objective of ...

BACKGROUND We aimed to assess RET proto-oncogene polymorphisms in three different Iranian families with medullary thyroid cancer (MTC), and performed molecular dynamics simulations and free energy stability analysis of these mutations. MATERIALS AND METHODS This study consisted of 48 patients and their first-degree relatives with MTC confirmed by pathologic diagnosis and surgery. We performed...

127 Multiple endocrine neoplasia type 2 (MEN2) syndromes are autosomally dominant clinical associations characterised by a number of tumours, including medullary thyroid carcinoma (MTC), phaeochromocytoma, thyroid C-cell hyperplasia (CCH), parathyroid tumours (MEN2A) and ganglioneuroma of the gastrointestinal tract (MEN2B). The common factor in the MEN2 syndromes is MTC, a poorly differentiated...

Multiple endocrine neoplasia type 2 (MEN 2) is a genetic syndrome caused by germline mutations in the RET proto-oncogene. These mutations cause changes in either the cysteine-rich extracellular domain or, less commonly, the non-cysteine intracellular domains of the RET protein. The genotype-phenotype correlations of classical cysteine RET mutations have been the subject of several comprehensive...

Constitutive activation of the Rearranged during Transfection (RET) proto-oncogene leads to the development of MEN2A medullary thyroid cancer (MTC). The relatively clear genotype/phenotype relationship seen with RET mutations and the development of MEN2A is unusual in the fact that a single gene activity can drive the progression towards metastatic disease. Despite knowing the oncogene responsi...