The data suggested that the expression of BANCR may promote the development of malignant thyroid nodules via the modulation of TSHR expression and its downstream effector, cyclin D1.
To examine the association of TSHR mutations with the functional status and surgical outcomes of thyroid nodules, we evaluated 703 consecutive thyroid FNA samples with indeterminate cytology for TSHR mutations using next-generation sequencing.
The role of methylation status of the thyroid stimulating hormone receptor gene (TSHr) in the discrimination of benign and malignant thyroid nodules has already been studied using paraffin blocks and cell lines.
Lack of association between autonomously functioning thyroid nodules and germline polymorphisms of the thyrotropin receptor and Gαs genes in a mild to moderate iodine-deficient Caucasian population.
Deletion of thyrotropin receptor residue Asp403 in a hyperfunctioning thyroid nodule provides insight into the role of the ectodomain in ligand-induced receptor activation.
The I630L mutation of the TSHR gene occurs not only at somatic level in toxic thyroid nodules, but also its presence in germline is associated with nonautoimmune primary hyperthyroidism.
Gain-of-function mutations in the TSH receptor and the Galpha(S) subunit occur frequently in hyperfunctioning thyroid nodules and differentiated thyroid carcinomas, whereby the T allele of a common polymorphism (825C>T, rs5443) in the G protein beta3 subunit gene (GNB3) is associated with increased G protein-mediated signal transduction and a complex phenotype.
We measured TSHR mRNA levels by RT-PCR in 258 subjects: 51 healthy subjects and 207 patients (thyroid nodules, n = 180; recurrent thyroid cancer, n = 27) with fine-needle aspirations (FNA) and/or thyroid/neck surgery.
Similar prevalence of somatic TSH receptor and Gsalpha mutations in toxic thyroid nodules in geographical regions with different iodine supply in Turkey.
Follicular carcinoma presenting as autonomous functioning thyroid nodule and containing an activating mutation of the TSH receptor (T620I) and a mutation of the Ki-RAS (G12C) genes.
Mutations in the thyrotropin receptor signal transduction pathway in the hyperfunctioning thyroid nodules from multinodular goiters: a study in the Turkish population.
The functional activity of the thyroid nodules prompted us to screen for TSH receptor (TSHR) mutations, and the histological diagnosis of follicular carcinoma led us to search for the PAX8-PPARgamma1 rearrangement and mutations in the ras genes.
For instance, mutations of the gsp and thyroid-stimulating hormone receptor genes are associated with benign hyperfunctioning thyroid nodules and adenomas while alterations of other specific genes, such as oncogenic tyrosine kinase alterations (RET/PTC, TRK) in papillary carcinoma and the newly discovered PAX8/peroxisome proliferator-activated receptor gamma rearrangement, are distinctive features of cancer.
These constitutively activating somatic TSH-receptor mutations in minute autoradiographically hot areas of euthyroid goiters are very likely starting foci which most likely lead to toxic thyroid nodules in iodine-deficient goiters.
To investigate ras and TSH receptor mutations with respect to functional differentiation we studied 41 scintigraphically cold nodules and 47 toxic thyroid nodules.
Autonomously functioning thyroid nodules are characterized by an increased proliferation and function, which is predominantly caused by constitutively activating TSH receptor mutations leading to an activation of cAMP.
This is the first evidence that TSH receptor mutations occur in microscopic areas with increased (125)I-labelling in euthyroid goiters and it suggests that TSH receptor mutations in these areas confer the potential to develop into toxic thyroid nodules.