Here, we describe a novel missense mutation of the RET protooncogene that substitutes arginine for proline at codon 912 of the intracellular tyrosine kinase domain in a family with medullary thyroid carcinoma.
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).
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.
Penetrance of inherited medullary thyroid carcinoma and genotype-phenotype correlation in a large multiple endocrine neoplasia type 2A family with C634YRET mutation.
Sporadic MTC was defined as a lack of personal or family history suggestive of multiple endocrine neoplasia type 2 (MEN 2) and lack of germline RET mutations which define any MEN 2 subtype.
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.
Our results indicate that the cold SSCV method offers the advantages of simplicity, time savings, and nonradioactive detection for screening for RET sequence variants in hereditary and sporadic MTCs.
Data were collected on patients identified as carriers of the RET mutation or diagnosed with medullary thyroid carcinoma (MTC) and/or PHEO with family history from 52 institutions all over Japan.
Finally, point mutations of the RET gene are found in familial endocrine syndromes (FMTC; MEN2A and MEN2B), a common feature of which is the medullary thyroid carcinoma, a malignant tumor derived from parafollicular C-cells.
This study reports the smallest case of sporadic MTC with a double RET somatic mutation, substantiating that RET mutations can occur during a very early stage of carcinogenesis.
Considering that PTC is not an incidental finding, but the result of an inherited RET V804 M mutation, we propose to identify this phenotypic expression as a unique syndrome consistent with manifestations of MTC, PHPT, and PTC.
RET genotypes (exons 10, 11, 13, and 14) of 63 patients with hereditary MTC (from November 1994 to October 1999) were correlated with age at diagnosis, sex, the TNM system, and basal calcitonin levels.
Sequencing analysis of the RET proto-oncogene revealed a Cys634Trp (TGC->TGG) mutation in all clinically affected family members and in an asymptomatic 5-year-old child who, after thyroidectomy, was found to have multicentric medullary thyroid carcinoma and C-cell hyperplasia.
We demonstrate a novel mechanism for MTC aggressiveness in which mutated RET/NF-κB-driven expression of miR-182 impedes HES1 activation in a negative feedback loop.
Here we describe two new RET mutations/variants, R770Q and L881V, in patients with MTC and analyzed genotype-phenotype correlations associated with these RET mutations in the gene carriers.
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.
This review will provide a brief overview of MTC and the associated RET oncogenic mutations, and will summarize the therapies designed to strategically interfere with the pathologic activation of the RET oncogene.