Genetic abnormalities in sporadic parathyroid adenomas: Loss of heterozygosity for chromosome 3q markers flanking the calcium receptor locus

Journal Article · Sun Oct 01 04:00:00 EDT 1995 · Journal of Clinical Endocrinology and Metabolism

DOI:https://doi.org/10.1210/jc.80.11.3377· OSTI ID:443621

Thompson, D B; Samowitz, W S; Davis, K ^[1]

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1. Univ. of Utah School of Medicine, Salt Lake City, UT (United States); and others

Inactivating mutations of the parathyroid cell calcium receptor (CaR) gene cause one form of familial benign/hypocalciuric hypercalcemia, and in homozygous form, cause neonatal severe primary hyperparathyroidism with parathyroid hyperplasia. Thus, we postulated that partial or total loss of CaR function might contribute to calcium insensitivity or even stimulate cell proliferation in sporadic parathyroid adenomas (PAds). To examine this possibility, we sought loss of heterozygosity (LOH) for markers flanking the CaR locus (3cen-3q21) in 35 PAds. We used 16 highly-polymorphic PCR-based markers in paired normal and tumor DNA, extracted from archived surgical specimens. Nineteen to twenty-four of the DNA pairs were informative with at least one marker. In two informative pairs, we found LOH for markers D3S1303, D3S1267, or D3S1269, which are tightly-linked with and flank the CaR locus. In one tumor, deletion mapping confined the lost area between D3S1271 and D3S1238 (41.7 centimorgans, cM). In the other tumor, LOH spanned most of chromosome 3, ranging at least from D3S1307 to D3S1311 (271.4 cM). LOH was confirmed by repetition of the experiments and quantified by phosphorimaging. Thus, we found LOH encompassing the CaR locus in approximately 10% of sporadic PAds. These data are consistent with the hypothesis that loss of CaR function may occur in PAds, with functional consequences for calcium sensitivity and cell proliferation. 20 refs., 2 figs.

• OSTI ID: 443621
• Journal Information: Journal of Clinical Endocrinology and Metabolism, Journal Name: Journal of Clinical Endocrinology and Metabolism Journal Issue: 10 Vol. 80; ISSN JCEMAZ; ISSN 0021-972X
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
ADENOMAS
BIOLOGICAL MARKERS
CALCIUM
CELL PROLIFERATION
GENE MUTATIONS
GENES
GENETIC MAPPING
HUMAN CHROMOSOME 3
PARATHYROID GLANDS
POLYMERASE CHAIN REACTION
RECEPTORS
STATISTICS
STRUCTURE-ACTIVITY RELATIONSHIPS