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- Starker, Lee F., et al.
(författare)
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Evidence of a stabilizing mutation of beta-catenin encoded by CTNNB1 exon 3 in a large series of sporadic parathyroid adenomas
- 2012
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Ingår i: Endocrine. - : Springer Science and Business Media LLC. - 1355-008X .- 1559-0100. ; 42:3, s. 612-615
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Tidskriftsartikel (refereegranskat)abstract
- Aberrant accumulation of beta-catenin plays an important role in a variety of human neoplasms. This can be caused by stabilizing mutation of beta-catenin (CTNNB1, exon 3) or by mutation or deregulated expression of other components of the WNT/beta-catenin signaling pathway. Accumulation of non-phosphorylated active beta-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 (LRP5 Delta) or to a stabilizing mutation of beta-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 beta-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 beta-catenin stabilization, enhanced transcription, and oncogenic activities. Immunohistochemical analysis revealed an overexpression of the beta-catenin protein in the lone mutant tumor. Taking also previous studies into account we conclude that activating mutations of the regulatory GSK-3 beta phosphorylation sites serine 33 and 37, encoded by CTNNB1 exon 3, rarely occur in parathyroid adenomas from patients with pHPT.
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