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...

CONTEXT Medullary and papillary thyroid carcinoma (MTC and PTC) are two types of thyroid cancer that can originate from activating mutations or rearrangements in the RET gene. Therapeutic options are limited in recurrent disease, but because RET is a tyrosine kinase (TK) receptor involved in cellular growth and proliferation, treatment with a TK inhibitor might be promising. Several TK inhibito...

BACKGROUND Screening medullary thyroid carcinomas (MTCs) for rearranged during transfection (RET) mutations becomes increasingly important for clinical assessment of the disease. The role of mutations in other genes including RAS (i.e. HRAS, KRAS, and NRAS), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), v-akt murine thymoma viral oncogene homolog 1 (AKT1), and CTNNB1 (β-catenin) is unk...

The familial risk of medullary thyroid carcinoma (MTC alone or as part of multiple endocrine neoplasms, MEN2A/MEN2B) is high, so we aimed to answer open questions about the lifetime cumulative risk of thyroid cancer (LCRTC at 0-79 years) among relatives of MTC patients by age and sex. For this nationwide study, a cohort of 3217 first-/second-degree relatives (FDRs/SDRs) of 389 MTC patients diag...

The catalytic and signaling activities of RET, a receptor-type tyrosine kinase, are regulated by the autophosphorylation of several tyrosine residues in the cytoplasmic region of RET. Some studies have revealed a few possible autophosphorylation sites of RET by [(32)P]phosphopeptide mapping or by using specific anti-phosphotyrosine antibodies. To ultimately identify these and other autophosphor...

BACKGROUND Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant inherited endocrine malignancy syndrome. Early and normative surgery is the only curative method for MEN 2-related medullary thyroid carcinoma (MTC). In patients with adrenal pheochromocytoma, cortical-sparing adrenalectomy (CSA) can be utilized to preserve adrenocortical function. METHODS We present twenty-six of ...

Medullary thyroid carcinoma occurs most often as a sporadic malignancy, although in approximately 30% of cases, it occurs as part of the multiple endocrine neoplasia type 2 (MEN2) syndromes MEN2A and MEN2B or the related disease, familial medullary thyroid carcinoma. These three syndromes, inherited as autosomal dominant traits, are clinically characterized by near complete penetrance but varia...