Distinct clinical phenotypes in a family with a novel truncating MEN1 frameshift mutation.

Background: MEN1 mutations can inactivate or disrupt menin function and are leading to multiple endocrine neoplasia type 1, a rare heritable tumor syndrome.

Case Presentation: We report on a MEN1 family with a novel heterozygous germline mutation, c.674delG; p.

Multiple endocrine neoplasia type 1 associated with a new germline Men1 mutation in a family with atypical tumor phenotype.

Background: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal-dominant hereditary disorder associated with the development of endocrine tumors due to reduced expression of the tumor suppressor protein menin. Recent studies indicate a general role of menin in carcinogenesis, affecting the prevalence and clinical course of common non-endocrine tumors such as breast cancer, hepatocellular carcinoma and melanoma. Here we report a new germline missense mutation of Men1 in a German family with atypical tumor phenotype over three generations.

Prevalence and clinical spectrum of nonsecretory medullary thyroid carcinoma in a series of 839 patients with sporadic medullary thyroid carcinoma.

Background: Medullary thyroid carcinoma (MTC) is characterized by the synthesis and secretion of calcitonin (Ct). MTC without Ct secretion has been reported on rare occasions. The aim of this study was to analyze the prevalence and clinical spectrum of nonsecretory MTC in two tertiary centers that cared for 839 patients with sporadic MTC.

Clinical relevance of RET variants G691S, L769L, S836S and S904S to sporadic medullary thyroid cancer.

Background: Based on reports of higher frequencies among patients with sporadic medullary thyroid cancer (MTC) relative to external controls, the RET (REarranged during Transfection) variants G691S, L767L, S836S and S904S have been considered disease modifiers, suggesting greater lifetime risks of MTC. Other studies, employing different external controls, failed to confirm this association. Using a complementary approach, this study aimed at exploring differences in clinico-pathological characteristics among patients with sporadic MTC carrying no (wildtype), one (heterozygotes) or both (homozygotes) homologue RET variants in the germline, with wildtype cases acting as internal controls.

Molecular genetics and phenomics of RET mutations: Impact on prognosis of MTC.

Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant hereditary cancer syndrome caused by missense gain-of-function mutations of the RET proto-oncogene. Three distinct clinical subtypes of MEN 2 have been characterized: MEN 2A, MEN 2B, and familial medullary thyroid carcinoma (FMTC). The specific RET mutation may suggest a predilection toward a particular phenotype and clinical course, with strong genotype-phenotype correlations.

Characterization of the RET protooncogene transmembrane domain mutation S649L associated with nonaggressive medullary thyroid carcinoma.

Context: For rare and novel RET mutations associated with hereditary medullary thyroid carcinoma (MTC), clinical and functional studies are needed to classify the RET mutation into one of the three clinical risk groups.

Objective: We analyzed proliferative properties and clinical implications associated with the RET protooncogene transmembrane domain mutation S649L.

Design: The transforming potential and mitogenic properties of S649L mutation were investigated clinically and by evaluating kinase activity, cell proliferation, and colony formation.

Change in the spectrum of RET mutations diagnosed between 1994 and 2006.

Medullary thyroid carcinoma (MTC) is a rare calcitonin producing tumor. About 70-75% of patients with MTC have sporadic disease while the others suffer from hereditary MTC. Hereditary MTC is divided into three clinical subtypes: multiple endocrine neoplasia (MEN) type 2A is characterized by MTC, pheochromocytoma and primary hyperparathyroidism.

Coincidence of multiple endocrine neoplasia types 1 and 2: mutations in the RET protooncogene and MEN1 tumor suppressor gene in a family presenting with recurrent primary hyperparathyroidism.

Context: Primary hyperparathyroidism (HPT) presents as a part of inherited syndromes such as multiple endocrine neoplasia (MEN) types 1 and 2. In patients with MEN1, parathyroid hyperplasia or multiple adenomas occur in approximately 90-95%. MEN2A-related HPT is characterized by a mild hypercalcemia, which is mostly asymptomatic.