The heritable MTC results from a germline mutation in the rearranged during transfection (RET) proto-oncogene and is included into the multiple endocrine neoplasia 2 (MEN2), being associated with other endocrine abnormalities and clinical features.
Structural and metastatic recurrence is common in patients with germline RET mutations, and MTC and can occur 20 years after initial treatment, however survival remains high.
In conclusion, these data indicate that an unbalanced cofilin expression, induced by oncogenic RET, contributes to promote MTC invasiveness and growth, suggesting the possibility of targeting cofilin pathway for more effective treatment of MTC.
We recruited 50 out of 350 MTC plasma samples (27 female and 23 male) which were selected based on RET mutation in exon 11 (25 RET-positive and 25 RET-negative), with a mean ± SD age of 37.04 ± 1.74 years.
Since early surgery with complete resection of tumor mostly determines the likelihood of attaining cure for MTC, the broader use of RET genetic screening has dramatically changed the prognostic of gene carriers in hereditary MTC.
To analyze the long-term outcomes in MEN2 and compare MTC aggressiveness in three defined RET mutation-risk categories: moderate risk (MOD), high risk (H), and highest risk (HST).
p.Ser891AlaRET gene mutations in medullary thyroid cancer: Phenotypical and genealogical characterization of 28 apparently unrelated kindreds and founder effect uncovering in Northern Italy.
Thirty-three percent were diagnosed with benign nodules (n=151), 36% with papillary or follicular thyroid cancer (n=168), 27% with Graves' disease (n=124), 3% with medullary thyroid cancer (n=14), and 1.5% underwent prophylactic thyroidectomy for MEN2a (n=7).
We report here that RET(C618F), a mutation identified in MTC patients, displays moderately high basal activity and requires the ligand for its full activation.
In this study, we collected clinical and molecular data from 554 patients with surgically confirmed MTC from 176 families with MEN2 in 18 different Brazilian centers to compare the type and prevalence of RET mutations with those from other countries.
Medical records and laboratory reports of carriers were reviewed for signs of MEN2A at latest follow-up (medullary thyroid carcinoma, primary hyperparathyroidism, pheochromocytoma, cutaneous lichen amyloidosis, or Hirschsprung's disease).
MEN1 is characterized by the occurrence of parathyroid, enteropancreatic, and pituitary tumors; MEN2A is characterized by medullary thyroid carcinoma and pheochromocytoma, and MEN4 is characterized by a pathological spectrum similar to that of MEN1 in association with tumors of the adrenal, kidney, and reproductive organs.
Expression analysis found an increase of RET transcript in p.Cys630=;p.Cys634Arg patient compared with that found in 7 MTCs harboring p.Cys634 mutations.
The remaining 15 RET mutation carriers did not exhibit CLA; of these, one presented with MTC and pheochromocytoma, nine with MTC only, two with elevated serum calcitonin and three younger subjects with normal serum calcitonin levels.
Metastatic medullary thyroid cancer (MTC) is incurable and FDA-approved kinase inhibitors that include oncogenic RET as a target do not result in complete responses.
The remaining 15 RET mutation carriers did not exhibit CLA; of these, 1 presented with MTC and pheochromocytoma, 9 with MTC only, 2 with elevated serum calcitonin, and 3 younger subjects with normal serum calcitonin levels.
We evaluated the prevalence of rearranged during transfection gene mutation in patients who have medullary thyroid carcinoma and the correlations of genotype with medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism according to the revised American Thyroid Association risk level.