Alu elements mediate MYB gene tandem duplication in human T-ALL.
Alu elements mediate MYB gene tandem duplication in human T-ALL.
复制标题
Alu元素介导了人类T-All中的MyB基因串联重复。
DOI：
10.1084/jem.20071637
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发表时间：
2007-12-24
影响因子：
15.3
通讯作者：
Look, A Thomas
中科院分区：
文献类型：
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作者：
O'Neil, Jennifer;Tchinda, Joelle;Gutierrez, Alejandro;Moreau, Lisa;Maser, Richard S;Wong, Kwok-Kin;Li, Wei;McKenna, Keith;Liu, X Shirley;Feng, Bin;Neuberg, Donna;Silverman, Lewis;DeAngelo, Daniel J;Kutok, Jeffery L;Rothstein, Rodney;DePinho, Ronald A;Chin, Lynda;Lee, Charles;Look, A Thomas
最近的研究表明，MYB癌基因在人类T细胞急性淋巴细胞白血病（T- all）中经常重复。我们发现人类MYB基因座两侧有257 bp的Alu重复序列，这种重复是通过姐妹染色单体上两侧Alu元件之间的同源重组介导的。巢式远程PCR分析表明，在50%的健康人的外周血单核细胞中，同源重组的频率较低，导致MYB串联重复，而这些健康人在种系中都没有MYB重复。我们得出结论，alu介导的MYB串联复制在正常胸腺细胞发育过程中以低频率发生，并在人类T-ALL的分子发病过程中被克隆选择。
Recent studies have demonstrated that the MYB oncogene is frequently duplicated in human T cell acute lymphoblastic leukemia (T-ALL). We find that the human MYB locus is flanked by 257-bp Alu repeats and that the duplication is mediated somatically by homologous recombination between the flanking Alu elements on sister chromatids. Nested long-range PCR analysis indicated a low frequency of homologous recombination leading to MYB tandem duplication in the peripheral blood mononuclear cells of ∼50% of healthy individuals, none of whom had a MYB duplication in the germline. We conclude that Alu-mediated MYB tandem duplication occurs at low frequency during normal thymocyte development and is clonally selected during the molecular pathogenesis of human T-ALL.