MOLECULAR BIOLOGIC STUDIES ON THE CAUSE OF PARATHYROID NEOPLASIA

原发性甲状旁腺功能亢进症(HPT)是一种常见的内分泌疾病 HAT可导致严重的肾脏和 骨骼系统。甲状旁腺功能亢进可能是由于良性肿瘤的单个 甲状旁腺(腺瘤)、良性肿瘤累及多发 甲状旁腺(增生性)，极少数为恶性 甲状旁腺肿瘤(癌)。该病的病因学 甲状旁腺肿瘤尚未定义，但临床和 流行病学研究表明，增生性疾病通常是由于 遗传性缺陷(多发性内分泌肿瘤1型和2型)，以及 头部和颈部受过放射史与 患甲状旁腺肿瘤的风险显著增加。AS 对于其他形式的肿瘤，甲状旁腺肿瘤可能是 由于遗传(生殖系突变)和/或获得性(体细胞突变) 突变)特定基因的缺陷。病因性遗传缺陷 可能包括转化“癌基因”的不适当表达 和/或肿瘤“抑制”基因的表达缺失。这个 手术切除的甲状旁腺肿瘤的可用性使我们能够 去寻找肿瘤特有的基因异常 参与甲状旁腺肿瘤的发展。首字母 这项工作的阶段包括比较基因组印迹 甲状旁腺肿瘤DNA和外周血白细胞DNA 耐心等待重新排列或删除。在即将推出的探测器中 用于表达的基因(例如甲状旁腺激素基因) 在甲状旁腺组织中处于高水平；这些基因的重排 可能会导致不适当地表达先前确定的或 新的致癌基因。此外，对编码基因等基因的探针 维生素D受体可以检测到取消表达的缺失 指一种基因，该基因的产物可以阻止细胞的异常分裂。

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.