title: Oncogenic mutations in the thyrotropin receptor of autonomously functioning thyroid nodules in the Japanese population.
abstract: OBJECTIVE
  Constitutively activating mutations of the thyrotropin receptor (TSHR) have been found in the majority of autonomously functioning thyroid nodules (AFTNs) in European patients. The reported frequency of these mutations varies among reports but amounts to 50-80%. To date, only one such mutation responsible for AFTNs has been identified in the Japanese population and the pathogenic role of such mutations in Japanese AFTNs has been questioned. In the present study, we evaluated the frequency of activating mutations in the TSHR and G(alpha)s in 10 Japanese AFTNs.
  
  
  METHODS
  Genomic DNA was extracted from fresh frozen tissue. The TSHR and the almost entire sequence of the gene coding for the alpha subunit of Gs have been amplified and sequenced.
  
  
  RESULTS
  In sequence analysis, four mutations in the TSHR (T632A, I486M, M453T and L512R) were found. To complete our analysis, we searched mutations in the gene coding for the alpha subunit of Gs, in the samples negative for TSHR mutations. In one case a mutation (R201H) affecting GTPase activity was found.
  
  
  CONCLUSIONS
  If we focus on the solitary nodules, we obtain the same mutation proportion as in European patients (70%). The absence of TSHR and G(alpha)s mutations in a significant proportion of autonomous adenomas in multinodular goiters suggests that other causes may also play a role in the genesis of these lesions.
authors.affiliation: Institute of Interdisciplinary Research, University of Brussels, Campus Erasme, Route de Lennik 808, B-1070 Brussels, Belgium. vvvooren@ulb.ac.be
authors.forename: V
authors.initials: V
authors.lastname: Vanvooren
authors.forename: S
authors.initials: S
authors.lastname: Uchino
authors.forename: L
authors.initials: L
authors.lastname: Duprez
authors.forename: M J
authors.initials: MJ
authors.lastname: Costa
authors.forename: J
authors.initials: J
authors.lastname: Vandekerckhove
authors.forename: J
authors.initials: J
authors.lastname: Parma
authors.forename: G
authors.initials: G
authors.lastname: Vassart
authors.forename: J E
authors.initials: JE
authors.lastname: Dumont
authors.forename: J
authors.initials: J
authors.lastname: Van Sande
authors.forename: S
authors.initials: S
authors.lastname: Noguchi
mesh_terms: D004247:DNA / Q000032:analysis; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics; D006801:Humans; D007564:Japan; D008297:Male; D009154:Mutation; D011989:Receptors, Thyrotropin / Q000235:genetics*; D017422:Sequence Analysis, DNA; D016606:Thyroid Nodule / Q000235:genetics*
chemical_list: D011989:Receptors, Thyrotropin; D004247:DNA; D019205:GTP-Binding Protein alpha Subunits, Gs