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.
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.
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).
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.
p.Ser891AlaRET gene mutations in medullary thyroid cancer: Phenotypical and genealogical characterization of 28 apparently unrelated kindreds and founder effect uncovering in Northern Italy.
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.
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.
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.
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).
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).
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.
MEN2B is mainly characterized by the early occurrence of MTC, which led the American Thyroid Association to recommend preventive thyroidectomy before the age of 1 year.
In the present study, we investigated whether the oncogenic RET mutants RET2A (C634R) and RET2B (M918T) were regulated by LRIG1, and the possible effects of LRIG1 expression in thyroid cancer were investigated in three different clinical cohorts and in a RET2B-driven mouse model of MTC.
Patients who died because of MTC had a median age of 61 years (range 21-84) and were at stages III-IV in all cases; deaths occurred in 18% of sporadic MTC, 6% of MEN2a and 66.7% of MEN2b patients.
In first-in-human testing, BLU-667 significantly inhibited RET signaling and induced durable clinical responses in patients with <i>RET</i>-altered NSCLC and MTC without notable off-target toxicity, providing clinical validation for selective RET targeting.<b>Significance:</b> Patients with <i>RET</i>-driven cancers derive limited benefit from available MKIs.