MONOCLONALITY AND ABNORMAL PARATHYROID-HORMONE GENES IN PARATHYROID ADENOMAS

MONOCLONALITY AND ABNORMAL PARATHYROID-HORMONE GENES IN PARATHYROID ADENOMAS
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DOI:
10.1056/nejm198803173181102
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发表时间:
1988-03-17
影响因子:
158.5
通讯作者:
KRONENBERG, HM
KRONENBERG, HM
中科院分区:
医学1区
文献类型:
--
作者:
ARNOLD, A;STAUNTON, CE;KRONENBERG, HM

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以前的工作基于葡萄糖-6-磷酸脱氢酶同工酶的相对组织含量,表明甲状旁腺腺瘤,像原发性增生,可能是多细胞腺瘤,像原发性增生,可能是多细胞(非克隆)起源。我们用两种独立的分子遗传学方法重新检查了该组织。我们报告的肿瘤细胞特异性限制片段长度的变化涉及甲状旁腺激素基因从两个人甲状旁腺腺瘤。这些异常的限制性片段表明,在每种情况下,克隆增殖的细胞是存在的,也表明,DNA的改变涉及甲状旁腺激素位点可能是重要的肿瘤发生或克隆进化的一些甲状旁腺腺瘤。此外,我们使用X连锁基因(次黄嘌呤磷酸核糖转移酶)的限制性片段长度多态性来研究8例女性甲状旁腺腺瘤的克隆性。在这8个腺瘤中,6个具有单克隆的DNA杂交模式,2个具有不确定的模式。五个增生的甲状旁腺没有一个是单克隆的。我们的结论是,一些(也许是许多)单一的甲状旁腺腺瘤是单克隆肿瘤。我们的观察结果表明,甲状旁腺腺瘤和原发性增生之间有一个基本的生物学差异。sbd。一个差异,可以证明在临床上区分这些实体有用。
Previous work based on the relative tissue content of glucose-6-phosphate dehydrogenase isoenzymes suggested that parathyroid adenomas, like primary hyperplasia, may be multicellular adenomas, like primary hyperplasia, may be multicellular (not clonal) in origin. We have reexamined this tissue by using two independent molecular genetic methods. We report tumor-cell-specific restriction-fragment-length alterations involving the parathyroid hormone gene from two human parathyroid adenomas. These abnormal restriction fragments indicate that in each case a clonal proliferation of cells was present and also suggest that DNA alterations involving the parathyroid hormone locus may be important in the tumorigenesis or clonal evolution of some parathyroid adenomas. In addition, we used a restriction-fragment-length polymorphism in an X-linked gene (hypoxanthine phosphoribosyltransferase) to examine the clonality of eight parathyroid adenomas in women. Of these eight adenomas, six had the DNA hybridization pattern of monoclonality, and two had an equivocal pattern. None of five hyperplastic parathyroid glands had a monoclonal pattern. We conclude that some (and perhaps many) single parathyroid adenomas are monoclonal neoplasms. Our observations suggest that there is a fundamental biologic difference between parathyroid adenomas and primary hyperplasia.sbd.a difference that could prove useful in distinguishing these entities clinically.