MOLECULAR-CLONING AND CHROMOSOMAL MAPPING OF DNA REARRANGED WITH THE PARATHYROID-HORMONE GENE IN A PARATHYROID ADENOMA
MOLECULAR-CLONING AND CHROMOSOMAL MAPPING OF DNA REARRANGED WITH THE PARATHYROID-HORMONE GENE IN A PARATHYROID ADENOMA
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DOI：
10.1172/jci114114
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发表时间：
1989-06-01
影响因子：
15.9
通讯作者：
KRONENBERG, HM
中科院分区：
文献类型：
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作者：
ARNOLD, A;KIM, HG;KRONENBERG, HM
甲状旁腺腺瘤是一种常见的良性肿瘤，其染色体无异常。我们最近发现两个甲状旁腺腺瘤携带涉及PTH位点的克隆性限制性片段异常，现在表明在其中一个肿瘤中：（a）在PTH位点发生DNA重排;（B）重排将PTH基因的5“侧翼区与其编码外显子分离，可以想象将一个新的相邻基因置于PTH调控元件的影响下;（c）与PTH重组的DNA通常定位于11 q13，这是几种致癌基因和I型多发性内分泌瘤的基因的已知染色体位置;和（d）该重组是11 q13上的基因座（人类基因定位文库分配D11 S287）与PTH（在11 p15上）的相互保守重组。这些数据为良性甲状旁腺肿瘤11号染色体的克隆性异常提供了分子细胞遗传学证据。D11 S287克隆可用于遗传连锁分析，确定其他肿瘤中精确的11 q13断裂点，以及鉴定11号染色体上可能参与甲状旁腺肿瘤发展的基因。
Parathyroid adenomas are common benign neoplasms for which no chromosomal defects have been described. We recently found two parathyroid adenomas bearing clonal restriction fragment abnormalities involving the PTH locus, and now show that in one of these tumors: (a) a DNA rearrangement occurred at the PTH locus; (b) the rearrangement separated the PTH gene''s 5'' flanking region from its coding exons, conceivably placing a newly adjacent gene under the influence of PTH regulatory elements; (c) the DNA that recombined with PTH normally maps to 11q13, the known chromosomal location of several oncogenes and the gene for multiple endocrine neoplasia type I; and (d) the rearrangment was a reciprocal, conservative recombination of the locus on 11q13 (human Gene Mapping Library assignment D11S287) with PTH (on 11p15). These data provide molecular cytogenetic evidence for the clonal occurrence of a major chromosome 11 aberrancy in this benign parathyroid tumor. The D11S287 clone could prove useful in genetic linkage analyses, in determining precise 11q13 breakpoints in other neoplasms, and in identifying a gene on chromosome 11 that may participate in parathyroid tumor development.