Fernández-Serra A, Rubio-Briones J, García-Casado Z, Solsona E, López-Guerrero J A
Laboratorio de Biología Molecular, Fundación Instituto Valenciano de Oncología, Valencia, España.
Actas Urol Esp. 2011 Jul-Aug;35(7):420-8. doi: 10.1016/j.acuro.2010.11.019. Epub 2011 May 23.
TMPRSS2-ETS fusion gene rearrangements constitute a very common and specific alteration in prostate cancer cells. These genetic alterations lead the overexpression of ETS genes which encode the E26 family of transcription factors involved in cell proliferation. Of this family, the ERG oncogene is overexpressed in almost 50% of prostate cancer cases.
TMPRSS2-ERG overexpresses ERG through an androgen-mediated response. Structurally, the rearrangement is due to interstitial deletion and to a lesser extent to reciprocal translocation and plays a key role in cellular metabolism. Almost all fusion gene transcripts produce a truncated ERG protein and the presence of a specific isoform of this gene suggests the clonality of the tumor; hence, metastasis shares the fusion gene status of their primary lesion. Although the prognostic implications of TMPRSS2-ERG have not been fully elucidated, they constitutes a field of great diagnostic potential and, therefore, the development of techniques to identify and to analyze the presence and characteristics of this gene in a non-invasive fashion deserves great interest in this area. Currently, there is evidence supporting the hypothesis that the presence of fusion gene differentiates two molecular groups within prostate cancer with a differential behaviour making the fusion gene a potential therapeutic target. In this regard, the use of anti-HDAC (trichostatin), antagonists of estrogen receptor alpha and abiraterone acetate have shown promising results.
This review describes the great potential offered by the investigation of fusion genes in PC and the need for further studies.
TMPRSS2-ETS融合基因重排是前列腺癌细胞中一种非常常见且特异的改变。这些基因改变导致ETS基因的过表达，ETS基因编码参与细胞增殖的E26转录因子家族。在这个家族中，ERG癌基因在近50%的前列腺癌病例中过表达。
TMPRSS2-ERG通过雄激素介导的反应使ERG过表达。在结构上，重排是由于间质性缺失，在较小程度上是由于相互易位，并且在细胞代谢中起关键作用。几乎所有的融合基因转录本都会产生截短的ERG蛋白，该基因特定异构体的存在提示肿瘤的克隆性；因此，转移灶与其原发灶具有相同的融合基因状态。尽管TMPRSS2-ERG的预后意义尚未完全阐明，但它们具有很大的诊断潜力，因此，开发以非侵入性方式识别和分析该基因的存在及其特征的技术在该领域备受关注。目前，有证据支持这样的假设，即融合基因的存在将前列腺癌分为两个分子亚组，它们具有不同的行为，这使得融合基因成为一个潜在的治疗靶点。在这方面，使用抗HDAC（曲古抑菌素）、雌激素受体α拮抗剂和醋酸阿比特龙已显示出有前景的结果。
本综述描述了研究前列腺癌融合基因所提供的巨大潜力以及进一步研究的必要性。
