Agarwal S K, Schröck E, Kester M B, Burns A L, Heffess C S, Ried T, Marx S J
Genetics and Endocrinology Section, NIH, NIDDK, Bethesda, Maryland, USA.
Cancer Genet Cytogenet. 1998 Oct 1;106(1):30-6. doi: 10.1016/s0165-4608(98)00049-1.
Primary hyperparathyroidism is characterized by hypercalcemia and elevated parathyroid hormone levels. It can be caused by overactivity of one (adenoma or carcinoma) or more (hyperplasia or multiple adenoma) parathyroid glands. Parathyroid adenoma and hyperplasia are usually mono- or oligoclonal neoplasms. To establish whether parathyroid cancer has a genetic composition distinct from parathyroid adenoma, we analyzed 10 adenoma and 10 carcinoma cases by comparative genomic hybridization (CGH). Results show clear differences between the constitution of adenoma and carcinoma genomic DNA. The most frequent genomic alterations in adenoma included deletions on chromosomes 11, 17 (5 of 10 cases), and 22 (7 of 10 cases). In parathyroid carcinoma, frequent chromosomal deletions were on chromosome arm 1p (4 of 10 cases) and chromosome 17 (3 of 10 cases), and gains were on chromosome 5 (3 of 10 cases). Our data indicate that different genetic changes could contribute to the development of parathyroid adenoma and carcinoma; genomic losses predominate in adenoma, and gains along with some losses are found in carcinoma. Furthermore, the CGH results implicate several chromosomal regions that may harbor genes that could be potentially involved in the development of parathyroid adenoma and carcinoma.
原发性甲状旁腺功能亢进症的特征是高钙血症和甲状旁腺激素水平升高。它可能由一个(腺瘤或癌)或多个(增生或多发性腺瘤)甲状旁腺的过度活跃引起。甲状旁腺腺瘤和增生通常是单克隆或寡克隆性肿瘤。为了确定甲状旁腺癌是否具有与甲状旁腺腺瘤不同的基因组成,我们通过比较基因组杂交(CGH)分析了10例腺瘤和10例癌病例。结果显示腺瘤和癌基因组DNA组成之间存在明显差异。腺瘤中最常见的基因组改变包括11号、17号(10例中有5例)和22号染色体(10例中有7例)的缺失。在甲状旁腺癌中,常见的染色体缺失发生在1p染色体臂(10例中有4例)和17号染色体(10例中有3例),而5号染色体出现增益(10例中有3例)。我们的数据表明,不同的基因变化可能导致甲状旁腺腺瘤和癌的发生;基因组缺失在腺瘤中占主导,而在癌中则发现有增益以及一些缺失。此外,CGH结果表明几个染色体区域可能含有可能参与甲状旁腺腺瘤和癌发生的基因。