Thyrotropin receptor mutations in hyperfunctioning thyroid adenomas from Brazil.

Détails

ID Serval
serval:BIB_ECB7A5B72E84
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Thyrotropin receptor mutations in hyperfunctioning thyroid adenomas from Brazil.
Périodique
Thyroid
Auteur⸱e⸱s
Nogueira C.R., Kopp P., Arseven O.K., Santos C.L., Jameson J.L., Medeiros-Neto G.
ISSN
1050-7256 (Print)
ISSN-L
1050-7256
Statut éditorial
Publié
Date de publication
11/1999
Peer-reviewed
Oui
Volume
9
Numéro
11
Pages
1063-1068
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
Publication Status: ppublish
Résumé
Constitutively activating mutations in the thyrotropin (TSH) receptor have been identified as a major molecular cause of hyperfunctioning thyroid adenomas. A smaller subset of these benign tumors is caused by constitutive activation of the adenylyl cyclase cascade by somatic mutations in the Gsalpha gene. In this study, we analyzed hyperfunctioning thyroid adenomas from seven Brazilian patients for TSH receptor and G(s)alpha gene mutations. Solitary autonomous thyroid adenomas were identified by ultrasound and scintigraphy, and DNA was extracted from adenomatous and periadenomatous tissue. Exons 9 and 10 of the TSH receptor gene, and exons 8 and 9 of the G(s)alpha gene, were amplified by polymerase chain reaction (PCR) and subjected to direct sequence analysis. Six of seven adenomas harbored heterozygous mutations known to confer constitutive activity to the TSH receptor. In one case, aspartate 619 was substituted by glycine (D619G). In four adenomas, alanine 623 was replaced by valine (A623V). Both residues are located in the third intracellular loop. In one instance, aspartate 633 located in the sixth transmembrane domain was replaced by tyrosine (D633Y). In this patient, one allele also contained a change of aspartate 727 to glutamate (D727E). This substitution is thought to be a polymorphic variant of the wild-type but it has also been associated with toxic multinodular goiters. Functional comparison of D727 with E727 did not reveal differences in basal or TSH-stimulated cyclic adenosine monophosphate (cAMP)-dependent luciferase activity in transiently transfected cells. These results demonstrate a high prevalence of activating TSH receptor mutations in toxic adenomas in this small series from Brazil (approximately 86%). These findings are in agreement with reports from other countries with a marginal iodine intake but contrast with studies from regions with a high iodine intake where these mutations appear to be less prevalent.
Mots-clé
Adenoma/genetics, Base Sequence, DNA/chemistry, Humans, Luciferases/metabolism, Mutation, Receptors, Thyrotropin/genetics, Thyroid Neoplasms/genetics
Pubmed
Web of science
Création de la notice
30/12/2020 15:21
Dernière modification de la notice
31/12/2020 6:26
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