MOLECULAR BIOLOGIC STUDIES ON THE CAUSE OF PARATHYROID NEOPLASIA

Primary hyperparathyroidism (HPT) is a common endocrine disorder hat can cause significant morbidity involving the renal and skeletal systems. HPT may be due to benign neoplasia of a single parathyroid gland (adenoma), benign neoplasia involving multiple parathyroid glands (hyperplasia), and rarely, to malignant neoplasia of a parathyroid gland (carcinoma). The etiology of parathyroid neoplasia has not been defined, but clinical and epidemiologic studies indicate that hyperplasia is often due to an inherited defect (multiple endocrine neoplasia types 1 and 2), and that a history of head and neck irradiation is associated with a significantly higher risk of developing parathyroid neoplasia. As with other forms of neoplasia, parathyroid tumors are presumably due to inherited (germ-line mutation) and/or acquired (somatic mutation) defects in specific genes. Etiologic genetic defects could include inappropriate expression of transforming "oncogenes" and/or loss of expression of tumor "suppressor" genes. The availability of surgically resected parathyroid tumors allows us to search for tumor-specific genetic abnormalities that may be involved in development of parathyroid neoplasia. The initial phase of this work involves comparison of genomic blots of parathyroid tumor DNA and peripheral leukocyte DNA from the same patient for rearrangements or deletions. Among the probes to be used are those for genes (e.g. parathyroid hormone gene) expressed at high levels in parathyroid tissue; rearrangements of such genes could lead to inappropriate expression of previously identified or novel oncogenes. Also, probes for genes such as that encoding the vitamin D receptor could detect deletions that abolish expression of a gene whose product prevents abnormal cell division.