Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York 10021, USA.
Genome Res. 2011 Jan;21(1):56-67. doi: 10.1101/gr.110684.110. Epub 2010 Oct 29.
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.
一半的前列腺癌中存在 TMPRSS2 和 ETS 转录因子家族成员之间的基因融合。迄今为止，对于前列腺癌中非 ETS 融合事件的存在知之甚少。我们使用下一代转录组测序（RNA-seq）技术，以探索 25 个人类前列腺癌样本的整个转录组中嵌合融合转录本的存在。我们生成了超过 10 亿个序列读段，并使用了一种新颖的计算方法（FusionSeq），以高可信度识别新的基因融合候选物。总共，我们发现并表征了七个新的癌症特异性基因融合，其中两个涉及 ETS 基因 ETV1 和 ERG，四个涉及非 ETS 基因，如 CDKN1A（p21）、CD9 和 IKBKB（IKK-beta），这些基因已知在细胞稳态中发挥关键生物学作用，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 RSRC2。这些新的基因融合的频率较低，但有趣的是，非 ETS 融合均存在于携带有 TMPRSS2-ERG 基因融合的前列腺癌中。未来的工作将集中于确定前列腺癌中的 ETS 重排是否与易发生重排的表型相关或直接导致该表型。
