title: Thyrotropin receptor gene alterations in thyroid hyperfunctioning adenomas.
abstract: Forty-four thyroid autonomously hyperfunctioning adenomas were analyzed to assess the frequency of mutations occurring in the TSH receptor (TSHR). PCR-amplified fragments encompassing the entire exon 10 of the TSHR gene were obtained from the genomic DNA extracted from the tumors and their adjacent normal tissues and were examined by direct nucleotide sequencing. Point mutations were found in 9 of the 44 adenomas examined (20%). One mutation occurred in codon 619 (Asp to Gly), four in codon 623 (three were Ala to Ser, one Ala to Val substitution), two in codon 632 (both Thr to Ile), and two in codon 633 (Asp to Tyr or His). All the alterations were located in a part of the gene coding for an area including the third intracellular loop and the sixth transmembrane domain of the TSH receptor. All mutations were somatic and heterozygotic, and none was simultaneous with alterations of ras or gsp oncogenes. Thus, our data show that in our series of 44 hyperfunctioning thyroid adenomas, a somatic mutation of the TSHR, responsible for the constitutive activation of the cAMP pathway, occurs in 20% of the tumors.
authors.affiliation: Dipartimento di Medicina Sperimentale e Clinica, Catanzaro, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Russo
authors.forename: F
authors.initials: F
authors.lastname: Arturi
authors.forename: H G
authors.initials: HG
authors.lastname: Suarez
authors.forename: M
authors.initials: M
authors.lastname: Schlumberger
authors.forename: J A
authors.initials: JA
authors.lastname: Du Villard
authors.forename: U
authors.initials: U
authors.lastname: Crocetti
authors.forename: S
authors.initials: S
authors.lastname: Filetti
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000503:physiopathology / Q000601:surgery; D000595:Amino Acid Sequence; D001483:Base Sequence; D003062:Codon / Q000235:genetics; D017931:DNA Primers; D005091:Exons; D005787:Gene Frequency; D006801:Humans; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011989:Receptors, Thyrotropin / Q000235:genetics*; D013961:Thyroid Gland / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000503:physiopathology / Q000601:surgery
chemical_list: D003062:Codon; D017931:DNA Primers; D011989:Receptors, Thyrotropin