Dysregulation of cyclin dependent kinase 6 expression in splenic marginal zone lymphoma through chromosome 7q translocations
Dysregulation of cyclin dependent kinase 6 expression in splenic marginal zone lymphoma through chromosome 7q translocations
复制标题
DOI：
10.1038/sj.onc.1203033
复制
发表时间：
1999-11-04
期刊：
影响因子：
8
通讯作者：
Oscier, DG
中科院分区：
文献类型：
--
作者：
Corcoran, MM;Mould, SJ;Oscier, DG
通过特异性染色体易位，具有致癌特性的基因的增加或不适当表达是B细胞淋巴增生性疾病发病机制中的重要事件。最近的研究发现，染色体7 q的缺失或易位是在SMZL的白血病变体SLVL中观察到的最常见的细胞遗传学异常，其中q21-q22区域最常受到影响。在3名2号和7号染色体之间易位的患者中，对7 q21处断点的克隆显示，每个断点都位于细胞周期蛋白依赖性激酶6（CDK 6）转录起始位点上游3.6 kb的一小段DNA区域内。在每种情况下，易位事件与染色体2 p12上的免疫球蛋白轻链区（IG κ）和7 q21处的DNA序列之间的异常VJ重组一致，类似于七聚体重组位点。t（7; 21）断裂点，位于t（2;7）断裂点端粒的66 kb处，并与CDK 6和未表征的转录物并列。在两个SLVL患者样品中，发现CDK 6蛋白显著过表达。这些结果表明，CDK 6基因表达失调有助于SLVL和SMZL的发病机制。
The increased or inappropriate expression of genes with oncogenic properties through specific chromosome translocations is an important event in the pathogenesis of B-cell lymphoproliferative diseases. Recent studies have found deletions or translocations of chromosome 7q to be the most common cytogenetic abnormality observed in SLVL, a leukemic variant of SMZL, with the q21-q22 region being most frequently affected. In three patients with translocations between chromosomes 2 and 7, the cloning of the breakpoints at 7q21 revealed that each was located within a small region of DNA 3.6 kb upstream of the transcription start site of cyclin dependent kinase 6 (CDK6). In each case the translocation event was consistent with aberrant VJ recombination between the immunoglobulin light chain region (Ig kappa) on chromosome 2p12 and DNA sequences at 7q21, resembling the heptamer recombination site. The t(7;21) breakpoint in an additional patient with splenic marginal zone lymphoma (SMZL), resided 66 kb telomeric to the t(2;7) breakpoints juxtaposing CDK6 to an uncharacterized transcript. In two of the SLVL patient samples, the CDK6 protein was found to be markedly over expressed. These results suggest that dysregulation of CDK6 gene expression contributes to the pathogenesis of SLVL and SMZL.