Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Constitutively activating mutations have recently been identified in the thyrotropin receptor (TSHR) of hyperfunctioning thyroid adenomas and familial hyperthyroidism. In the present study, we evaluated the frequency of constitutively activating TSHR mutations in a large series of autonomously functioning thyroid nodules (AFTNs) in Japan. Forty-five AFTNs (38 solitary hyperfunctioning thyroid adenomas and 7 toxic multinodular goiters) were analyzed. Genomic DNA was extracted from paraffin-embedded tissue sections, from which DNA fragments encoding the mutational hot spots of the receptor (the third cytoplasmic loop and the sixth transmembrane segment) were amplified by polymerase chain reaction. In the single-stranded conformation polymorphism (SSCP) analysis, only one hyperfunctioning adenoma (no. 21) displayed a migration abnormality. In sequence analysis, an unusual mutation of alternate three-base deletions at nucleotides 1953-1957 (AAA GAT ACC to AAG TCC), resulting in one amino acid deletion (Asp at 619) and one conservative amino acid substitution (Thr to Ser at 620), was identified in tumor DNA but not in leukocyte DNA of no. 21. Further, the normal sequence in these regions was confirmed in 10 randomly selected samples with normal migrating patterns in SSCP analysis. The functional property of the mutant with delta 619 and T620S (designated TSHR delta 619) was then evaluated with in vitro mutagenesis and transfection studies. Unexpectedly, however, there were no significant differences in TSH binding affinity, and basal and TSH-stimulated levels of cAMP and inositol 1,4,5-triphosphate between the TSHR delta 619 and the wt-TSHR. In conclusion, the incidence of the constitutively activating TSHR mutations in AFTNs appears to be low in Japan. The oncogenic potential of a novel somatic mutant TSHR delta 619 identified in a hyperfunctioning adenoma in this study is at present uncertain because of its intact function.
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PMID:Rarity of oncogenic mutations in the thyrotropin receptor of autonomously functioning thyroid nodules in Japan. 767 2

The results of experiments carried out in different laboratories (including ours) during the last 10 years have enabled us to propose the hypothesis that there are different initiators able to start the epithelial thyroid tumorigenic process via different pathways:--gsp and TSHR genes: at the origin of hyperfunctioning tumors (toxic nodules and adenomas);--ras and probably gsp genes (in a minority of samples): via a vesicular adenoma progressing eventually to a vesicular carcinoma. This could be also the case for ret but only in radiation-associated tumours;--ras, ret, trk and probably gsp and met: starting from small papillary lesions ('spontaneous' or radiation-induced) and progressing to a clinically evident papillary carcinoma;--the p53 gene playing a role only in the final dedifferentiation process. Simultaneous alteration in the same sample of combinations of ras, gsp, ret, trk and TSHR was found in only a minority of the approximately 150 tumours studied. These data suggest an interchangeable role for these genes in the initiation of 'spontaneous' or radiation-associated epithelial thyroid tumorigenesis. The requirement of one of the genes cited above to interact with other genes must not be neglected. Ras is the most frequently altered gene in 'spontaneous' thyroid tumours and ret in radiation-associated thyroid tumours.
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PMID:Molecular basis of epithelial thyroid tumorigenesis. 1092 7

Epidermal growth factor (EGF) has widespread growth effects, and in some tissues proliferation is associated with the nuclear localization of EGF and epidermal growth factor receptor (EGFR). In the thyroid, EGF promotes growth but differs from thyrotropin (TSH) in inhibiting rather than stimulating functional parameters. We have therefore studied the occurrence and cellular distribution of EGF and EGFR in normal thyroid, in Graves' disease, where growth is mediated through the thyrotropin receptor (TSHR), and in a variety of human thyroid tumors. In the normal gland the staining was variable, but largely cytoplasmic, for both EGF and EGFR. In Graves' disease there was strong cytoplasmic staining for both EGF and EGFR, with frequent positive nuclei. Nuclear positivity for EGF and particularly for EGFR was also a feature of both follicular adenomas and follicular carcinomas. Interestingly, nuclear staining was almost absent in papillary carcinomas. These findings document for the first time the presence of nuclear EGF and EGFR in thyroid. Their predominant occurrence in tissues with increased growth (Graves' disease, follicular adenoma, and carcinoma) may indicate that nuclear EGF and EGFR play a role in growth regulation in these conditions. The absence of nuclear EGF and EGFR in papillary carcinomas would suggest that the role played by EGF in growth control differs between papillary carcinoma and follicular adenomas/carcinomas of the thyroid.
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PMID:Nuclear localization of epidermal growth factor and epidermal growth factor receptors in human thyroid tissues. 1128 82

Several mutations of the TSH-receptor gene have been described in a variety of thyroid diseases. Particularly in children and adolescents, somatic or germ cell mutations may lead to hyperthyroidism. In these cases, molecular analysis of the TSHR gene provides important information for further clinical management. We report a 3-year-old boy with a rare somatic TSHR mutation causing autonomous adenoma of the thyroid gland in order to illustrate how the genetic analysis of the lesion impacted on the surgical strategy. The patient presented with a left neck mass, negative thyroid autoantibodies, and unifocal autonomy on thyroid scan. He underwent local resection of the adenoma. Genetic workup demonstrated a somatic mutation of TSHR. Exons 9 and 10 of the TSHR gene (chromosome 14q3) from peripheral blood DNA and toxic thyroid adenoma tissue DNA were amplified by PCR and analyzed by denatured gradient gel electrophoresis (DGGE). DGGE from the EDTA blood sample showed no difference compared to the wild-type, whereas material extracted from the tissue sample showed a mutation in exon 10. Direct sequencing of the PCR product from the tissue demonstrated a heterozygous mutation in codon 453 (ATG-->ACG), leading to a substitution of methionine by threonine. The genetic appraisal of resected thyroid tissue in cases with nonautoimmune hyperthyroidism is important to formulate surgical and medical treatment plans. In cases with somatic mutations of the TSHR, simple resection of the adenoma is sufficient, whereas total thyroidectomy should be considered in patients with germ cell mutations.
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PMID:Activating TSH-receptor mutation (Met453Thr) as a cause of adenomatous non-autoimmune hyperthyroidism in a 3-year-old boy. 1949 84

The development of molecular biomarkers (BMs) of follicular thyroid carcinoma is aimed at advancing diagnosis of follicular neoplasm, as histological examination of those tumors does not lend itself to definitive diagnosis of carcinoma. We assessed the relative levels of expression of 6 genes: CCND2, PCSK2, PLAB, RAP2A, TSHR, and IGF-1R in archived thyroid tissue. The quantitative real-time PCR analysis revealed a significant change in 3 genes: PSCK2 (a 22.4-fold decrease, P = 2.81E - 2), PLAB (an 8.3-fold increase, P = 9.81E - 12), and RAP2A (a 6.3-fold increase, P = 9.13E - 10) in carcinoma compared with adenoma. Expression of PCSK2 was equally low, PLAB was equally high, whereas RAP2A expression was significantly higher (25.9-fold, P = 0.039) in microdissected carcinoma cells that have invaded through the thyroid capsule and entered blood vessels than in thyroid tumor cells growing under the capsule. Thus, RAP2A appeared as a unique and worthy of further evaluation candidate BM associated with invasion of thyroid follicular cells.
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PMID:Rap2A Is Upregulated in Invasive Cells Dissected from Follicular Thyroid Cancer. 2204 76