title: Does a Leu 512 Arg thyrotropin receptor mutation cause an autonomously functioning papillary carcinoma?
abstract: In the last decade, studies were first done to determine the frequency of Gsalpha and later thyrotropin receptor (TSHR) mutations in benign autonomously functioning thyroid nodules (AFTN). Different frequencies ranging from 0% to 38% for GSp mutations and from 20% to 86% for TSHR mutations were found. There were only some limited case reports related to TSHR genetic alterations in malignant AFTN. Their role in autonomously functioning thyroid carcinomas is not well established. We present a patient who had thyroidectomy for toxic multinodular goiter and a papillary carcinoma was demonstrated histopathologically. Genomic DNA was isolated from two solid areas in the hot nodule and peripheral leukocytes of the patient. After amplifying the related regions, TSHR and GSalpha genes were analyzed by single-strand conformation polymorphism (SSCP) analysis. The precise localization of the mutations was identified by automatic DNA sequence analysis. An activating mutation of the TSHR gene (Leu 512 Arg) was found in the autonomously functioning papillary carcinoma. It is believed that this mutation causes constitutive activation of the cyclic adenosine monophosphate (cAMP) signal transduction pathway and thereby causes thyrotoxicosis and a hot thyroid nodule in an autonomously functioning papillary carcinoma.
authors.affiliation: Section of Endocrinology and Metabolism, Marmara University Medical School, Istanbul, Turkey. hgozu@hotmail.com
authors.forename: Hulya
authors.initials: H
authors.lastname: Gozu
authors.forename: Melike
authors.initials: M
authors.lastname: Avsar
authors.forename: Rifat
authors.initials: R
authors.lastname: Bircan
authors.forename: Serap
authors.initials: S
authors.lastname: Sahin
authors.forename: Rengin
authors.initials: R
authors.lastname: Ahiskanali
authors.forename: Bahadir
authors.initials: B
authors.lastname: Gulluoglu
authors.forename: Oguzhan
authors.initials: O
authors.lastname: Deyneli
authors.forename: Tunc
authors.initials: T
authors.lastname: Ones
authors.forename: Yavuz
authors.initials: Y
authors.lastname: Narin
authors.forename: Sema
authors.initials: S
authors.lastname: Akalin
authors.forename: Beyazit
authors.initials: B
authors.lastname: Cirakoglu
mesh_terms: D000595:Amino Acid Sequence; D001120:Arginine; D001483:Base Sequence; D002291:Carcinoma, Papillary / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D005260:Female; D006044:Goiter, Nodular / Q000601:surgery; D006801:Humans; D007930:Leucine; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011877:Radionuclide Imaging; D011989:Receptors, Thyrotropin / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D013965:Thyroidectomy
chemical_list: D011989:Receptors, Thyrotropin; D001120:Arginine; D007930:Leucine