Tissue-specific regulatory regions of the PTH gene localized by novel chromosome 11 rearrangement breakpoints in a parathyroid adenoma.
Tissue-specific regulatory regions of the PTH gene localized by novel chromosome 11 rearrangement breakpoints in a parathyroid adenoma.
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DOI：
10.1002/jbmr.187
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发表时间：
2010-12
影响因子：
6.2
通讯作者：
Arnold, Andrew
中科院分区：
文献类型：
--
作者：
Mallya, Sanjay M.;Wu, H. Irene;Saria, Elizabeth A.;Corrado, Kristin R.;Arnold, Andrew
甲状旁腺腺瘤可以包含11号染色体的克隆重排，通过与PTH基因并列激活细胞周期蛋白D1癌基因。在这里，我们描述了这样一个染色体重排，其新的功能提供了线索，定位难以捉摸的顺式调节元件在PTH基因，也扩大了物理谱的发病断点在细胞周期蛋白D1基因区。Southern分析显示甲状旁腺腺瘤甲状旁腺素基因位点重排。通过筛选肿瘤基因组文库获得的含有断点的重排DNA克隆的分析，在第一外显子上游3.3 kb处的PTH基因座中精确定位断点。因此，PTH 5'调控区的高度保守的远端元件在细胞周期蛋白D1癌基因上游约450 kb的断裂点处重排，导致细胞周期蛋白D1 mRNA的过表达。因此，甲状旁腺肿瘤中的PTH-细胞周期蛋白D1基因重排断裂点可以远离那些以前认识到的。除了扩大在这种疾病中的致病性染色体病变的分子谱，这种特定的重排的功能，加强存在一个或多个新的顺式增强子/PTH基因表达的调控元件，并缩小其位置的1.7kb的DNA片段在远端PTH启动子。
Parathyroid adenomas can contain clonal rearrangements of chromosome 11 that activate the cyclin D1 oncogene through juxtaposition with the PTH gene. Here we describe such a chromosomal rearrangement whose novel features provide clues to locating elusive cis-regulatory elements in the PTH gene and also expand the physical spectrum of pathogenetic breakpoints in the cyclin D1 gene region. Southern analyses of the parathyroid adenoma revealed rearrangement in the PTH gene locus. Analysis of rearranged DNA clones that contained the breakpoint, obtained by screening a tumor genomic library, pinpointed the breakpoint in the PTH locus at 3.3 kb upstream of the first exon. Accordingly, highly conserved distal elements of the PTH 5’ regulatory region were rearranged at the breakpoint approximately 450 kb upstream of the cyclin D1 oncogene, resulting in overexpression of cyclin D1 mRNA. Thus, PTH-cyclin D1 gene rearrangement breakpoints in parathyroid tumors can be located far from those previously recognized. In addition to expanding the molecular spectrum of pathogenetic chromosomal lesions in this disease, features of this specific rearrangement reinforce the existence of one or more novel cis-enhancer/regulatory elements for PTH gene expression and narrow their location to a 1.7kb DNA segment in the distal PTH promoter.
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影响因子：
6.4
作者：
BARTKOVA, J;LUKAS, J;BARTEK, J
通讯作者：
BARTEK, J
影响因子：
158.5
作者：
ARNOLD, A;STAUNTON, CE;KRONENBERG, HM
通讯作者：
KRONENBERG, HM
影响因子：
4.8
作者：
Alimov, AP;Langub, MC;Koszewski, NJ
通讯作者：
Koszewski, NJ
影响因子：
15.9
作者：
ARNOLD, A;KIM, HG;KRONENBERG, HM
通讯作者：
KRONENBERG, HM
影响因子：
7
作者：
Couronne, O;Poliakov, A;Dubchak, I
通讯作者：
Dubchak, I