title: Evidence of a stabilizing mutation of β-catenin encoded by CTNNB1 exon 3 in a large series of sporadic parathyroid adenomas.
abstract: Aberrant accumulation of β-catenin plays an important role in a variety of human neoplasms. This can be caused by stabilizing mutation of β-catenin (CTNNB1, exon 3) or by mutation or deregulated expression of other components of the WNT/β-catenin signaling pathway. Accumulation of non-phosphorylated active β-catenin has been reported to commonly occur in parathyroid adenomas from patients with primary hyperparathyroidism (pHPT), either due to the aberrantly spliced internally truncated WNT receptor LRP5 (LRP5Δ) or to a stabilizing mutation of β-catenin. The S37A mutation was reported to occur in 7.3 % in a single study of parathyroid adenomas, while in other studies no stabilizing mutations of β-catenin exon 3 were identified. The aim of this study was to determine the mutational frequency of the CTNNB1 gene, specifically exon 3 in a large series of parathyroid adenomas. One hundred and eighty sporadic parathyroid adenomas were examined for mutations in exon 3 of CTNNB1 by direct DNA sequencing, utilizing previously published primer sequences. The mutation S33C (TCT>TGT) was detected by direct-DNA sequencing of PCR fragments in 1 out of 180 sporadic parathyroid adenomas (0.68 %). Like serine 37, mutations of serine 33 have been reported in many neoplasms with resulting β-catenin stabilization, enhanced transcription, and oncogenic activities. Immunohistochemical analysis revealed an overexpression of the β-catenin protein in the lone mutant tumor. Taking also previous studies into account we conclude that activating mutations of the regulatory GSK-3β phosphorylation sites serine 33 and 37, encoded by CTNNB1 exon 3, rarely occur in parathyroid adenomas from patients with pHPT.
authors.affiliation: Department of Surgery, Yale University School of Medicine, 330 Cedar Street, FMB 107, New Haven, CT, USA. Lee.Starker@yale.edu
authors.forename: Lee F
authors.initials: LF
authors.lastname: Starker
authors.forename: Annabelle L
authors.initials: AL
authors.lastname: Fonseca
authors.forename: Annabelle
authors.initials: A
authors.lastname: Fonseca
authors.forename: Göran
authors.initials: G
authors.lastname: Akerström
authors.forename: Peyman
authors.initials: P
authors.lastname: Björklund
authors.forename: Gunnar
authors.initials: G
authors.lastname: Westin
authors.forename: Tobias
authors.initials: T
authors.lastname: Carling
mesh_terms: D000236:Adenoma / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics* / Q000502:physiology*; D010282:Parathyroid Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D051176:beta Catenin / Q000235:genetics*
chemical_list: C495270:CTNNB1 protein, human; D051176:beta Catenin; D004247:DNA; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3