Multiple genomic alterations on 21q22 predict various TMPRSS2/ERG fusion transcripts in human prostate cancers
Multiple genomic alterations on 21q22 predict various TMPRSS2/ERG fusion transcripts in human prostate cancers
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DOI：
10.1002/gcc.20482
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发表时间：
2007-11-01
影响因子：
3.7
通讯作者：
Xu, Jianfeng
中科院分区：
文献类型：
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作者：
Liu, Wennuan;Ewing, Charles M.;Xu, Jianfeng
自从发现TMPRSS 2和ETS家族成员基因的融合导致反复的基因组重排以来，已经报道了许多TMPRSS 2/ERG融合转录物。在这篇文章中，我们提出的证据表明，多个基因组的改变有助于形成各种TMPRSS 2/ERG转录。通过对GeneChip 500 K SNP阵列生成的数据进行等位基因特异性分析，我们观察到前列腺癌中TMPRSS 2和ERG之间和内部的不同位置发生半合子和纯合子缺失。500 K SNP阵列使我们能够将每个缺失的开始和结束精细映射到这两个基因的特定内含子，并预测各种融合转录本，包括通过对各种肿瘤中融合转录本的序列分析证实的新形式。我们还推断，易位是这两个基因在一些肿瘤中融合的另一种机制，这主要是基于TMPRSS和ERG之间的二倍体基因组DNA，以及这些肿瘤中产生的不同融合转录本。使用生物信息学方法，我们发现了包含缺失断点的区域中的共有序列。这些共有序列与人的α-Sq和β-Sp亚家族共有序列同源性均在80%以上。TMPRSS 2和ERG基因内含子中Alu家族共有序列的存在/缺失与这两个基因的融合转录本的存在/缺失相关，表明这些共有序列可能有助于基因组缺失和TMPRSS 2与ERG的融合。(C)2007 Wiley-Liss，Inc.
A number of TMPRSS2/ERG fusion transcripts have been reported since the discovery that recurrent genomic rearrangements result in the fusion of TMPRSS2 and ETS family member genes. In this article we present evidence demonstrating that multiple genomic alterations contribute to the formation of various TMPRSS2/ERG transcripts. Using allele-specific analysis of the data generated from the GeneChip 500K SNP array we observed both hemizygous and homozygous deletions occurring at different locations between and within TMPRSS2 and ERG in prostate cancers. The 500K SNP array enabled us to fine map the start and end of each deletion to specific introns of these two genes, and to predict a variety of fusion transcripts, including a new form which was confirmed by sequence analysis of the fusion transcripts in various tumors. We also inferred that translocation is an additional mechanism of fusion for these two genes in some tumors, based on largely diploid genomic DNA between TMPRSS and ERG, and different fusion transcripts produced in these tumors. Using a bioinformatics approach, we then uncovered the consensus sequences in the regions harboring the breakpoints of the deletions. These consensus sequences were homologous to the human Alu-Sq and Alu-Sp subfamily consensus sequences, with more than 80% homology. The presence/absence of Alu family consensus sequence in the introns of TMPRSS2 and ERG correlates with the presence/absence of fusion transcripts of theses two genes, indicating that these consensus sequences may contribute to genomic deletions and the fusion of TMPRSS2 and ERG in prostate cancer. (C) 2007 Wiley-Liss, Inc.