Analysis of CYP27B1, encoding 25-hydroxyvitamin D-1alpha-hydroxylase, as a candidate tumor suppressor gene in primary and severe secondary/tertiary hyperparathyroidism.

CYP27B1, encoding 25-hydroxyvitamin D-1alpha-hydroxylase, converts 25-hydroxyvitamin D to its active form, 1,25-dihydroxyvitamin D, and is expressed primarily in the kidney but also in nontraditional sites including the parathyroid glands. Whereas the role of locally produced 1,25-dihydroxyvitamin D is not yet clear, it is possible that it contributes importantly to vitamin D-mediated inhibition of parathyroid cell growth, so CYP27B1 can be considered a candidate parathyroid tumor suppressor gene in that its acquired inactivation in a parathyroid cell could confer a tumorigenic growth advantage. Expression of CYP27B1 has also been reported to be altered in parathyroid neoplasms. Because detection of inactivating mutations is the central criterion for validating a candidate tumor suppressor, we directly sequenced the coding region and all splice sites of CYP27B1 in 31 sporadic parathyroid adenomas and 31 parathyroid tumors from patients with refractory secondary/tertiary hyperparathyroidism. No nonsense, frameshift, or other inactivating mutations were found, and there was no sign of homozygous deletion. Our findings indicate that CYP27B1 does not commonly serve as a classical tumor suppressor gene in the development of sporadic parathyroid adenomas or of refractory secondary/tertiary hyperparathyroidism.