Background & Aims: Thyroid cancer is the most common endocrine malignancy. Medullary thyroid carcinoma (MTC) is an aggressive malignant tumor arising from parafollicular cells of the thyroid. MTC occurs in hereditary (25%, hMTC) or sporadic (75%, sMTC) forms. The hMTC form has an autosomal dominant inheritance. RET proto-oncogene mutations, especially the 10, 11, and 16 exones, are associated w...

meduiiary thyroid carcinoma (mtc) occurs both sporadically and in the autosomal dominantly inherited multiple endocrine neoplasia (men) type 2 syndromes. the distinction between true sporadic mtc and a new mutation familial case is important for future clinical management of both the patient and family. the susceptibility gene for hereditary mtc is the ret proto-oncogene. dna analysis for germl...

Hereditary medullary thyroid carcinoma (MTC) is caused by autosomal dominant gain-of-function mutations in the RET proto-oncogene. Associations between specific RET mutations (genotype) and the aggressiveness of MTC and presence or absence of other endocrine neoplasms (phenotype) are well documented. Mutations in six exons (10, 11, 13, 14, 15, and 16) located in either cysteine-rich or tyrosine...

The RET proto-oncogene encodes a receptor tyrosine kinase expressed in neural crest derived tissues. Germline mutations in the RET proto-oncogene are responsible for three different dominantly inherited cancer syndromes: multiple endocrine neoplasia type 2A (MEN 2A), type 2B (MEN 2B), and familial medullary thyroid carcinoma (FMTC). MTC can also occur sporadically. Molecular characterisation of...

A family with germline tandem V804M/Y806C mutations in the RET proto-oncogene was reported. The in vitro study results showing that these mutations were on the same allele and that RET with these mutations had a moderate transforming activity were confirmed by the clinical features of the offspring as a natural experiment. Thus, the tandem double RET mutations are pathogenetic for MEN 2B.

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant disease characterized by the presence of medullary thyroid carcinoma, primary hyperparathyroidism, and pheochromocytoma. Multiple endocrine neoplasia type 2 is still an underdiagnosed, or late-diagnosed condition in many areas of the world. Since 1993, when the first missense RET proto-oncogene (RET) mutations were reported in ...

Activating mutations of the RET proto-oncogene cause hereditary medullary thyroid carcinoma. To examine whether selective inactivation of mutant RET could prevent transformation, a hammerhead ribozyme was designed to cleave RET mRNA containing a transforming mutation of codon 634 TGC --> TAC (Cys634Tyr). In vitro RNA cleavage assay demonstrated that the ribozyme selectively cleaved RET RNA with...

The RET proto-oncogene has been identified as the multiple endocrine neoplasia type 2 disease gene. An association between specific RET mutation and disease phenotype has been reported. We present the phenotype-genotype of 12 Greek families with multiple endocrine neoplasia type 2A (MEN 2A) or familial medullary thyroid carcinoma (FMTC). Seventy members were studied and DNA analysis for RET mut...

The ret proto-oncogene encodes a receptor tyrosine kinase with a cadherin-like motif in the extracellular domain. Recently, it turned out that ret is the causative gene for the development of multiple endocrine neoplasia (MEN) type 2A and type 2B and Hirschsprung's disease. MEN 2A and MEN 2B mutations represent activating changes of ret whereas Hirschsprung mutations inactivate ret. In addition...