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: Lee F Starker, Annabelle L Fonseca, Annabelle Fonseca, Göran Akerström, Peyman Björklund, Gunnar Westin, Tobias Carling
• Journal: Endocrine (Endocrine) Vol. 42 Issue 3 Pg. 612-5 (Dec 2012) ISSN: 1559-0100 [Electronic] United States
• PMID: 22576020 (Publication Type: Journal Article)

Chemical References

• CTNNB1 protein, human
• beta Catenin
• DNA
• GSK3B protein, human
• Glycogen Synthase Kinase 3 beta
• Glycogen Synthase Kinase 3

Topics

• Adenoma (genetics)
• DNA (genetics)
• Exons (genetics)
• Female
• Glycogen Synthase Kinase 3 (genetics)
• Glycogen Synthase Kinase 3 beta
• Humans
• Immunohistochemistry
• Male
• Middle Aged
• Mutation (genetics, physiology)
• Parathyroid Neoplasms (genetics)
• Polymerase Chain Reaction
• beta Catenin (genetics)