Db. Thompson et al., GENETIC ABNORMALITIES IN SPORADIC PARATHYROID ADENOMAS - LOSS OF HETEROZYGOSITY FOR CHROMOSOME 3Q MARKERS FLANKING THE CALCIUM RECEPTOR LOCUS, The Journal of clinical endocrinology and metabolism, 80(11), 1995, pp. 3377-3380
Inactivating mutations of the parathyroid cell calcium receptor (CaR)
gene cause one form of familial benign/hypocalciuric hypercalcemia, an
d in homozygous form, cause neonatal severe primary hyperparathyroidis
m with parathyroid hyperplasia. Thus, we postulated that partial or to
tal loss of CaR function might contribute to calcium insensitivity or
even stimulate cell proliferation in sporadic parathyroid adenomas (PA
ds). To examine this possibility, we sought loss of heterozygosity (LO
H) 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 slices of archived surgical specimens. Nineteen to 24
of the DNA pairs were informative with at least one marker. In two in
formative 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 chromo
some 3, ranging at least from D3S1307 to D3S1311 (271.4 cM). LOH was c
onfirmed by repetition of the experiments and quantified by phosphorim
aging. Thus, we found LOH encompassing the CaR locus in approximately
10% of sporadic PAds. These data are consistent with the hypothesis th
at loss of CaR function may occur in PAds, with functional consequence
s for calcium sensitivity and cell proliferation.