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Mol Cancer. 2008 Jun 9;7:53. doi: 10.1186/1476-4598-7-53.

Stabilizing mutation of CTNNB1/beta-catenin and protein accumulation analyzed in a large series of parathyroid tumors of Swedish patients.

Author information

1
Department of Surgical Sciences, Endocrine Unit, Uppsala University, Uppsala University Hospital, SE-751 85 Uppsala, Sweden. peyman.bjorklund@surgsci.uu.se

Abstract

BACKGROUND:

Aberrant accumulation of beta-catenin plays an important role in a variety of human neoplasms. We recently reported accumulation of beta-catenin in parathyroid adenomas from patients with primary hyperparathyroidism (pHPT). In CTNNB1 exon 3, we detected a stabilizing mutation (S37A) in 3 out of 20 analyzed adenomas. The aim of the present study was to determine the frequency and zygosity of mutations in CTNNB1 exon 3, and beta-catenin accumulation in a large series of parathyroid adenomas of Swedish patients.

RESULTS:

The mutation S37A (TCT > GCT) was detected by direct DNA sequencing of PCR fragments in 6 out of 104 sporadic parathyroid adenomas (5.8%). Taking our previous study into account, a total of 9 out of 124 (7.3%) adenomas displayed the same mutation. The mutations were homozygous by DNA sequencing, restriction enzyme cleavage, and gene copy number determination using the GeneChip 500 K Mapping Array Set. All tumors analyzed by immunohistochemistry, including those with mutation, displayed aberrant beta-catenin accumulation. Western blotting revealed a slightly higher expression level of beta-catenin and nonphosphorylated active beta-catenin in tumors with mutation compared to those without. Presence of the mutation was not related to distinct clinical characteristics.

CONCLUSION:

Aberrant accumulation of beta-catenin is very common in parathyroid tumors, and is caused by stabilizing homozygous mutation in 7.3% of Swedish pHPT patients.

PMID:
18541010
PMCID:
PMC2435117
DOI:
10.1186/1476-4598-7-53
[Indexed for MEDLINE]
Free PMC Article

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