No evidence for mutations in the calcium-sensing receptor gene in sporadicparathyroid adenomas

Inactivating mutations of the calcium-sensing receptor gene (CaR) might exp lain abnormalities in the regulation of both parathyroid cell proliferation and parathyroid hormone secretion. In a previous study, using RNAse A prot ection assay, no mutations were identified in a series of parathyroid speci mens from patients with primary and secondary hyperparathyroidism, but the analysis was incomplete, since part of exon 6 could not be analyzed. In the present study, we examined the presence of mutations in the CaR gene in 20 parathyroid adenomas using direct sequencing. The entire coding region of the CaR gene was successfully amplified by polymerase chain reaction and di rectly sequenced. This analysis did not identify CaR gene mutations in any tumors studied. A polymorphism that encoded a single amino acid change(Ala8 26Thr) was identified in 4 parathyroid adenomas and in 8 of 50 normal unrel ated subjects. Loss of heterozygosity studies were also performed on adenom as using markers for the locus of the CaR gene on chromosome 3q. No allelic loss was demonstrated, In conclusion, our results extend previous observat ion and suggest that clonal somatic mutations of the CaR gene and allelic l oss at the CaR locus on chromosome 3q do not play a major role in the patho genesis of sporadic parathyroid tumors.: