title: Low incidence of the stimulatory G protein alpha-subunit mutations in autonomously functioning thyroid adenomas in Japan.
abstract: Point mutations of the alpha-subunit of the stimulatory G protein (Gs alpha) (termed gsp) and the TSH receptor, leading to constitutive elevation of intracellular cAMP contents, have recently been described in autonomously functioning thyroid adenomas. Since we have recently found a clear difference in the incidence of such gain-of-function mutations of the TSH receptor between Japan and Europe, the present study was designed to evaluate the incidence of gsp mutations in a series of autonomously functioning thyroid adenomas in a Japanese population. Thirty-eight autonomously functioning thyroid adenomas were employed in the present study. Genomic DNA was extracted from archival formalin-fixed, paraffin-embedded tissue specimens. Exons 8 and 9 of the Gs alpha gene were examined for activating mutations at codons 201 and 227 by single-strand conformation polymorphism (SSCP) and nucleotide sequencing. Both exons 8 and 9 were successfully amplified in 28 of 38 samples by polymerase chain reaction. Of these only one sample for exon 9 displayed a distinct migration pattern in SSCP analysis, in which a point mutation of a G to C transversion was identified by nucleotide sequencing, resulting in substitution of His (CAC) for Gln (CAG) at codon 227. The wild-type sequence of exon 9 in 10 randomly selected samples with an identical migration pattern in SSCP analysis suggests that underestimation of the incidence of gsp mutations is unlikely in our work. In conclusion, the present data, together with our previous data on the TSH receptor, suggest that oncogenic mutations of the Gs alpha as well as the TSH receptor do not seem to play a major role in tumorigenesis of autonomously functioning thyroid adenomas in Japan.
authors.affiliation: Department of Pharmacology, Nagasaki University School of Medicine, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
authors.forename: Y
authors.initials: Y
authors.lastname: Nagayama
authors.forename: A
authors.initials: A
authors.lastname: Takeshita
authors.forename: H
authors.initials: H
authors.lastname: Namba
authors.forename: S
authors.initials: S
authors.lastname: Yamashita
authors.forename: M
authors.initials: M
authors.lastname: Niwa
authors.forename: S
authors.initials: S
authors.lastname: Nagataki
mesh_terms: D000236:Adenoma / Q000235:genetics*; D003062:Codon; D004247:DNA / Q000032:analysis; D019204:GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D007564:Japan; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011989:Receptors, Thyrotropin / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics*
chemical_list: D003062:Codon; D011989:Receptors, Thyrotropin; D004247:DNA; D019204:GTP-Binding Proteins