Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer
Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer
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DOI：
10.1126/science.1117679
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发表时间：
2005-10-28
期刊：
影响因子：
56.9
通讯作者：
Chinnaiyan, AM
中科院分区：
文献类型：
--
作者：
Tomlins, SA;Rhodes, DR;Chinnaiyan, AM
在常见的癌症中，复发性染色体重排还没有得到很好的表征。我们使用生物信息学的方法来发现候选致癌染色体畸变的基础上离群基因表达。两个ETS转录因子ERG和ETV1在前列腺癌中被鉴定为离群值。我们在具有异常表达的前列腺癌组织中鉴定了TMPRSS 2的5'非翻译区与ERG或ETV 1的复发性基因融合。通过使用荧光原位杂交，我们证明了29例前列腺癌样本中有23例在ERG或ETV1中存在重排。细胞系实验表明TMPRSS2的雄激素应答启动子元件介导前列腺癌中ETS家族成员的过表达。这些结果对前列腺癌的发生发展以及前列腺癌的分子诊断和治疗具有重要意义。
Recurrent chromosomal rearrangements have not been well characterized in common carcinomas. We used a bioinformatics approach to discover candidate oncogenic chromosomal aberrations on the basis of outlier gene expression. Two ETS transcription factors, ERG and ETV1, were identified as outliers in prostate cancer. We identified recurrent gene fusions of the 5' untranslated region of TMPRSS2 to ERG or ETV1 in prostate cancer tissues with outlier expression. By using fluorescence in situ hybridization, we demonstrated that 23 of 29 prostate cancer samples harbor rearrangements in ERG or ETV1. Cell line experiments suggest that the androgen-responsive promoter elements of TMPRSS2 mediate the overexpression of ETS family members in prostate cancer. These results have implications in the development of carcinomas and the molecular diagnosis and treatment of prostate cancer.