Medullary thyroid carcinomas (MTC) arise from thyroid parafollicular, calcitonin-producing C-cells and can occur either as sporadic or as hereditary diseases in the context of familial syndromes, including multiple endocrine neoplasia 2A (MEN2A), multiple endocrine neoplasia 2B (MEN2B) and familial MTC (FMTC).
We aim to identify RET mutations' (C634R and M918T) expression, location, and signaling activation during the disease's progression, which providing a theoretical basis for the study on etiology of multiple endocrine neoplasia.
Dominant-activating mutations in the RET proto-oncogene, a receptor tyrosine kinase, are responsible for the development of medullary thyroid carcinoma (MTC) and causative for multiple endocrine neoplasia (MEN) type 2A and 2B.
Four different MEN syndromes have been so far identified: MEN type 1 (MEN1), MEN2A (also referred to as MEN2), MEN2B (or MEN3) and MEN4, which have slightly varying tumor spectra and are caused by mutations in different genes.
The clinical characteristics and RET proto-oncogene (RET‑PO) mutation status of a patient with multiple endocrine neoplasia type 2A pedigree (MEN2A) was analyzed with the aim of preliminarily exploring the molecular mechanisms and clinical significance of the disease.
Molecular genetic studies in the past few years have identified >10 genes involved in the pathogenesis of pheochromocytomas and paragangliomas, including RET oncogene, involved in the pathogenesis of multiple endocrine neoplasia (MEN) 2A and 2B, von Hippel-Lindau tumor-suppressor gene, neurofibromatosis type 1 gene, succinate dehydrogenase, THEM127, and several others.
Bilateral pheochromocytoma (PHEO) is more frequently found in patients with multiple endocrine neoplasia 2A carrying a RET germline mutation located in codon 634 (C634).
Four major forms of MEN, which are autosomal dominant disorders, are recognized and referred to as: MEN type 1 (MEN1), due to menin mutations; MEN2 (previously MEN2A) due to mutations of a tyrosine kinase receptor encoded by the rearranged during transfection (RET) protoncogene; MEN3 (previously MEN2B) due to RET mutations; and MEN4 due to cyclin-dependent kinase inhibitor (CDNK1B) mutations.
American Thyroid Association (ATA) guidelines suggest that thyroidectomy can be delayed in some children with multiple endocrine neoplasia syndrome 2A (MEN2A) if serum calcitonin (Ct) and neck ultrasonography (US) are normal.
Over the last decade, our knowledge of the multiple endocrine neoplasia (MEN) type 2 syndromes MEN2A and MEN2B and familial medullary thyroid carcinoma (FMTC) has expanded greatly.
The mechanism whereby rearranged during transfection influences gene activation in multiple endocrine neoplasia 2 is complex, but genetic variations impair the rearranged during transfection tyrosine kinase response to tyrosine kinase activation, thus appearing to dictate downstream signaling cascade responses.
Patients with multiple endocrine neoplasia (MEN) type 2 with known RET gene mutations as well as those with other heritable disorders are candidates for PGD.
Germline mutations of RET gene are pathognomonic of multiple endocrine neoplasia (MEN; MEN 2A/MEN 2B) and familial medullary thyroid carcinoma (FMTC), constituting 25% of medullary thyroid carcinomas (MTCs).