MOLECULAR BIOLOGIC STUDIES ON THE CAUSE OF PARATHYROID NEOPLASIA

原发性甲状旁腺功能亢进症(HPT)，一种常见的内分泌疾病，可 引起明显的发病率，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)， 罕见的甲状旁腺恶性肿瘤(癌)。这个 甲状旁腺肿瘤的病因尚未确定。与其他产品一样 各种形式的肿瘤，甲状旁腺肿瘤可能是由于遗传性的 (胚系突变)和/或获得性(体细胞突变)缺陷 基因。病因性遗传缺陷可能包括不适当的表达 转化“癌基因”和/或肿瘤“抑制子”表达缺失 基因。手术切除甲状旁腺肿瘤的可行性 患有散发性和遗传性疾病的患者允许我们搜索 对于可能参与发展的肿瘤特有的遗传异常- 甲状旁腺肿瘤。我们发现了重新排列的 43例甲状旁腺腺瘤中只有1例携带甲状旁腺激素基因 基因异常可能与发病相关。与之相反， 在任何甲状旁腺肿瘤中均未发现ras癌基因突变。在……里面 遗传性多内分泌受试者的两个“增生性”腺体 I型肿瘤和散发性腺瘤的杂合性丢失 在染色体11q13上发现了1个基因座。数据显示，男性中的肿瘤是 是单克隆性的，而11q13中的一个基因座可能编码一个肿瘤“抑制子”。 吉恩。在其他方法中，我们正试图通过以下方式识别男性I基因 甲状旁腺肿瘤中11q13位点的定位缺失。

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.