Erschienen in:
01.02.2012 | Research Letter
A rare S33C mutation of CTNNB1 encoding β-catenin in a parathyroid adenoma found in an Italian primary hyperparathyroid cohort
verfasst von:
Vito Guarnieri, Filomena Baorda, Claudia Battista, Michele Bisceglia, Teresa Balsamo, Elisa Gruppioni, Michelangelo Fiorentino, Lucia A. Muscarella, Michelina Coco, Raffaela Barbano, Sabrina Corbetta, Anna Spada, David E. C. Cole, Lucie Canaff, Geoffrey N. Hendy, Massimo Carella, Alfredo Scillitani
Erschienen in:
Endocrine
|
Ausgabe 1/2012
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Excerpt
Primary hyperparathyroidism (PHPT) is one of the most common endocrine disorders with a prevalence of 21/1000 in women between 55 and 75 years of age, corresponding to a 3/1000 prevalence in the general population [
1]. Sporadic (non-familial) PHPT accounts for 90–95% of all cases. While activation of the protooncogene cyclin D1 (
CCDN1) and inactivation of the tumor suppressor menin gene (
MEN1) contribute to parathyroid adenomatosis, and inactivation of the parafibromin gene (
CDC73) contributes to parathyroid carcinogenesis, the molecular pathogenesis of these tumors is incompletely understood. Dysregulated Wnt signaling and activation of β-catenin is involved in several cancers and consequently there has been recent interest in whether this is implicated in parathyroid tumorigenesis. In the absence of Wnt, cytosolic β-catenin phosphorylation catalyzed by glycogen synthase kinase (GSK)-β on serine/threonine residues (S33, S37, T41) encoded by exon 3 of the
CTNNB1 gene leads to the ubiquitination and to degradation mediated by the proteasome. Mutation of the serine/threonine residues causes stabilization of the β-catenin protein and localization to the nucleus where it activates gene transcription. Several studies have been reported examining
CTNNB1 gene mutations and aberrant β-catenin localization in sporadic parathyroid adenomas. While studies from Sweden found the homozygous S37A mutation in ~7% of 124 parathyroid adenomas and aberrant β-catenin localization in all cases [
2,
3], other studies from Japan [
4,
5], USA [
6], Italy [
7], and Sweden [
8,
9] have failed to confirm these findings. Here, we report on our
CTNNB1 gene mutation analysis of parathyroid adenomas and carcinomas in a novel Italian PHPT cohort. …