Activating mutations of the RET proto-oncogene are associated with inherited syndromes, multiple endocrine neoplasia (MEN2A/2B) and with familial and sporadic medullary thyroid cancer (MTC). Single base pair missense mutations in the extracellular Cys-rich domain are responsible for most MEN2A and familial MTC (FMTC) cases. Rarely, somatic deletions and germline duplications have been described...

Although thyroid cancers are not among common malignancies, they rank as the first prevalent endocrine cancers in human. According to the results of published studies it has been shown the gradual progress from normal to the neoplastic cell in the process of tumor formation is the result of sequential genetic events. Among them we may point the mutations and rearrangements occurred in a group o...

A punch biopsy of one of the lingual papules revealed wellcircumscribed nodular lesions in the dermis, consisting of hyperplastic nerve fibers that were positive for neurofilament and S100 staining (Fig. 2). Based on these histological finding magnetic resonance imaging of the adrenal glands was performed, and levels of urine catecholamines and blood calcitonin were determined. All test results...

BACKGROUND Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor mainly caused by mutations in the rearranged during transfection (RET) proto-oncogene. Not all patients with progressive MTC respond to current therapy inhibiting RET, demanding additional therapeutic strategies. We recently demonstrated that disrupting mitochondrial metabolism using a mitochondria-targeted agent or by deple...

Background: The RET (rearranged during transfection) proto-oncogene codes for a tyrosine kinase receptor that plays an important role in the developmental regulation of the kidney and nervous systems. Sporadic mutations in RET have been well documented in cases of papillary thyroid carcinoma (PTC), the most common being RET/PTC 1 and RET/PTC 3. Although originally thought to be a specific tumor...

Multiple endocrine neoplasia type 2A (MEN2A), a subtype of MEN2, is characterized by medullary thyroid cancer, pheochromocytoma, and primary hyperparathyroidism. A Han Chinese pedigree with MEN2A was investigated following confirmation of the proband's diagnosis by pathological findings and DNA/biochemical screening. DNA samples from 4 other family members were collected and exon 5, 8, 10, 11, ...

Medullary thyroid cancer is frequently an aggressive form of carcinoma for which there are currently no effective forms of systemic therapy. These carcinomas arise as a result of activating mutations in the RET proto-oncogene transmembrane tyrosine kinase receptor. We, therefore, examined the potential efficacy of the tyrosine kinase inhibitor STI571 on the growth of human TT medullary cancer c...

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant tumour syndrome caused by germline activating mutations of the RET proto-oncogene. It has a strong penetrance of medullary thyroid carcinoma (MTC) and can be associated with bilateral pheochromocytoma and primary hyperparathyroidism (MEN2A) within a single patient or family. Based on the phenotype three distinct clinical forms ...

A punch biopsy of one of the lingual papules revealed wellcircumscribed nodular lesions in the dermis, consisting of hyperplastic nerve fibers that were positive for neurofilament and S100 staining (Fig. 2). Based on these histological finding magnetic resonance imaging of the adrenal glands was performed, and levels of urine catecholamines and blood calcitonin were determined. All test results...

Medullary thyroid cancer (MTC) is an aggressive malignancy responsible for up to 14% of all thyroid cancer-related deaths. It is characterized by point mutations in the rearranged during transfection (RET) proto-oncogene. The activated RET kinase is known to signal via extracellular signal regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K), leading to enhanced proliferation and resista...