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: 3855431
• 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/3855431
• 关键词: adenoma; chromosome aberrations; endocrine neoplasm; gene expression; human tissue; hyperparathyroidism; hyperplasia; molecular oncology; multiple endocrine neoplasia; neoplasm /cancer genetics; parathyroid neoplasms; point mutation; tumor suppressor genes

Primary hyperparathyroidism (HPT), a common endocrine disorder that can cause significant morbidity, may be due to benign neoplasia of a single parathyroid gland (adenoma) or multiple parathyroid glands (hyperplasia), and rarely, to malignant neoplasia of a parathyroid gland (carcinoma). The etiology of parathyroid neoplasia has not been defined. 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 from patients with sporadic and hereditary forms of disease allows us to search for tumor-specific genetic abnormalities that may be involved in develop- ment of parathyroid neoplasia. We have found rearrangement of the parathyroid hormone gene in only 1 of 43 parathyroid adenomas, but this gene abnormality may be pathogenetically relevant. In contrast, point mutations in ras oncogenes were not found in any parathyroid tumors. In both "hyperplastic" glands from subjects with inherited multiple endocrine neoplasia type I (MEN I) and in sporadic adenomas, loss of heterozygosity for loci on chromosome llql3 was found. The data show that tumors in MEN I are monoclonal, and that a locus in llql3 may encode a tumor "suppressor" gene. we are attempting to identify the MEN I gene among other methods by mapping deletions at llql3 in parathyroid tumors.

原发性甲状旁腺功能亢进（HPT）是一种常见的内分泌疾病， 引起显著的发病率，可能是由于良性肿瘤的单一 甲状旁腺（腺瘤）或多发性甲状旁腺（增生）， 很少发生甲状旁腺恶性肿瘤（癌）。 的 甲状旁腺肿瘤的病因尚未确定。 与其他 甲状旁腺肿瘤是一种肿瘤，可能是由于遗传 （生殖系突变）和/或获得性（体细胞突变）的特定缺陷， 基因. 病因遗传缺陷可能包括不适当的表达， 转化“癌基因”和/或肿瘤“抑制基因”表达缺失 基因. 手术切除甲状旁腺肿瘤的可行性 散发性和遗传性疾病的患者使我们能够搜索 肿瘤特异性遗传异常可能参与发展- 甲状旁腺瘤形成。 我们发现了 43例甲状旁腺腺瘤中只有1例有甲状旁腺激素基因，但这 基因异常可能与发病有关。 相反，点 在所有甲状旁腺肿瘤中均未发现ras癌基因突变。 在 这两个“增生”腺体都来自遗传性多内分泌 肿瘤I型（MEN I）和散发性腺瘤，杂合性丢失 结果表明，MEN I型肿瘤中， 是单克隆的，并且llql 3中的基因座可能编码肿瘤“抑制因子”， 基因我们正试图在其他方法中识别MEN I基因， 在甲状旁腺肿瘤中定位11 q13的缺失。