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


CONCLUSIONS
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.
Björklund
Peyman
P
Department of Surgical Sciences, Endocrine Unit, Uppsala University, Uppsala University Hospital, SE-751 85 Uppsala, Sweden. peyman.bjorklund@surgsci.uu.se
Lindberg
Daniel
D
Akerström
Göran
G
Westin
Gunnar
G
D000236:Adenoma / Q000737:chemistry / Q000235:genetics*; D015153:Blotting, Western; D004252:DNA Mutational Analysis; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D006720:Homozygote; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010282:Parathyroid Neoplasms / Q000737:chemistry / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D013548:Sweden; D015854:Up-Regulation; D051176:beta Catenin / Q000032:analysis / Q000235:genetics*
C495270:CTNNB1 protein, human; D051176:beta Catenin