MOLECULAR BIOLOGIC STUDIES ON THE CAUSE OF PARATHYROID NEOPLASIA

甲状旁腺肿瘤病因的分子生物学研究

• 批准号: 3918280
• 负责人: A SPIEGEL
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3918280
• 关键词: DNA; gene deletion mutation; gene expression; hormone related neoplasm /cancer; human tissue; hyperplasia; molecular oncology; neoplasm /cancer genetics; nucleic acid structure; oncogenes; parathyroid neoplasms; radiation related neoplasm /cancer

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.

原发性甲状旁腺功能亢进（HPT）是一种常见的内分泌疾病 它可引起涉及肾脏的显著发病率， 骨骼系统 HPT可能是由于良性肿瘤的单一 甲状旁腺（腺瘤），良性肿瘤，涉及多个 甲状旁腺（增生），很少，恶性 甲状旁腺瘤（癌）。 的病因 甲状旁腺肿瘤尚未定义，但临床和 流行病学研究表明，增生往往是由于 遗传缺陷（1型和2型多发性内分泌瘤），和 头部和颈部照射的历史与 发生甲状旁腺肿瘤的风险显著升高。 作为 与其他形式的肿瘤，甲状旁腺肿瘤大概是 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”基因表达的丧失。 的 手术切除的甲状旁腺肿瘤使我们能够 寻找肿瘤特异性基因异常， 参与甲状旁腺肿瘤的发展。 初始 这项工作的一个阶段涉及比较基因组印迹， 甲状旁腺肿瘤DNA及其外周血白细胞DNA 患者进行重排或缺失。 在探测器中， 所用的是表达的基因（例如甲状旁腺激素基因）的那些 在甲状旁腺组织中的高水平;这些基因的重排 可能导致先前确定的或 新癌基因 此外，用于基因的探针，例如编码 维生素D受体可以检测到缺失， 一种基因的产物可以阻止异常细胞分裂。