Discovery of non-ETS gene fusions in human prostate cancer using next-generation RNA sequencing
Discovery of non-ETS gene fusions in human prostate cancer using next-generation RNA sequencing
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DOI：
10.1101/gr.110684.110
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发表时间：
2011-01-01
期刊：
影响因子：
7
通讯作者：
Rubin, Mark A.
中科院分区：
文献类型：
--
作者：
Pflueger, Dorothee;Terry, Stephane;Rubin, Mark A.
一半的前列腺癌具有TMPRSS 2和ETS转录因子家族成员之间的基因融合。迄今为止，对前列腺癌中存在非ETS融合事件知之甚少。我们使用下一代转录组测序（RNA-seq）来探索25个人前列腺癌样本的整个转录组中是否存在嵌合融合转录物。我们生成了超过10亿个序列读段，并使用了一种新的计算方法（FusionSeq），以高置信度识别新的基因融合候选物。总的来说，我们发现并表征了七种新的癌症特异性基因融合，其中两种涉及ETS基因ETV 1和ERG，四种涉及非ETS基因，如CDKN 1A（p21），CD 9和IKBKB（IKK-β），这些基因已知在细胞内稳态中表现出关键的生物学作用或被认为在其他肿瘤实体的肿瘤发生中至关重要，以及致癌基因PIGU和肿瘤抑制基因RSRC 2。新的基因融合被发现是低频率的，但有趣的是，非ETS融合都存在于前列腺癌窝藏TMPRSS 2-ERG基因融合。未来的工作将集中在确定前列腺癌中ETS重排是否与复发倾向表型相关或直接易感。
Half of prostate cancers harbor gene fusions between TMPRSS2 and members of the ETS transcription factor family. To date, little is known about the presence of non-ETS fusion events in prostate cancer. We used next-generation transcriptome sequencing (RNA-seq) in order to explore the whole transcriptome of 25 human prostate cancer samples for the presence of chimeric fusion transcripts. We generated more than 1 billion sequence reads and used a novel computational approach (FusionSeq) in order to identify novel gene fusion candidates with high confidence. In total, we discovered and characterized seven new cancer-specific gene fusions, two involving the ETS genes ETV1 and ERG, and four involving non-ETS genes such as CDKN1A (p21), CD9, and IKBKB (IKK-beta), genes known to exhibit key biological roles in cellular homeostasis or assumed to be critical in tumorigenesis of other tumor entities, as well as the oncogene PIGU and the tumor suppressor gene RSRC2. The novel gene fusions are found to be of low frequency, but, interestingly, the non-ETS fusions were all present in prostate cancer harboring the TMPRSS2-ERG gene fusion. Future work will focus on determining if the ETS rearrangements in prostate cancer are associated or directly predispose to a rearrangement-prone phenotype.