Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.
Neoplasia. 2013 Jul;15(7):720-6. doi: 10.1593/neo.13232.
Gene fusions involving the erythroblast transformation-specific (ETS) transcription factors ERG, ETV1, ETV4, ETV5, and FLI1 are a common feature of prostate carcinomas (PCas). The most common upstream fusion partner described is the androgen-regulated prostate-specific gene TMPRSS2, most frequently with ERG, but additional 5' fusion partners have been described. We performed 5' rapid amplification of cDNA ends in 18 PCas with ETV1, ETV4, or ETV5 outlier expression to identify the 5' fusion partners. We also evaluated the exon-level expression profile of these ETS genes in 14 cases. We identified and confirmed by fluorescent in situ hybridization (FISH) and reverse transcription-polymerase chain reaction the two novel chimeric genes OR51E2-ETV1 and UBTF-ETV4 in two PCas. OR51E2 encodes a G-protein-coupled receptor that is overexpressed in PCas, whereas UBTF is a ubiquitously expressed gene encoding an HMG-box DNA-binding protein involved in ribosome biogenesis. We additionally describe two novel gene fusion combinations of previously described genes, namely, SLC45A3-ETV4 and HERVK17-ETV4. Finally, we found one PCa with TMPRSS2-ETV1, one with C15orf21-ETV1, one with EST14-ETV1, and two with 14q133-q21.1-ETV1. In nine PCas (eight ETV1 and one ETV5), exhibiting ETS outlier expression and genomic rearrangement detected by FISH, no 5' fusion partner was found. Our findings contribute significantly to characterize the heterogeneous group of ETS gene fusions and indicate that all genes described as 5' fusion partners with one ETS gene can most likely be rearranged with any of the other ETS genes involved in prostate carcinogenesis.
涉及红细胞生成素转化特异性（ETS）转录因子 ERG、ETV1、ETV4、ETV5 和 FLI1 的基因融合是前列腺癌（PCa）的一个常见特征。描述的最常见的上游融合伙伴是雄激素调节的前列腺特异性基因 TMPRSS2，最常与 ERG 融合，但也描述了其他 5' 融合伙伴。我们对 18 例 ETV1、ETV4 或 ETV5 表达异常的 PCa 进行了 5' 快速 cDNA 末端扩增，以确定 5' 融合伙伴。我们还评估了这 14 例 ETS 基因的外显子水平表达谱。我们通过荧光原位杂交（FISH）和逆转录-聚合酶链反应（RT-PCR）鉴定并证实了两个新的嵌合基因 OR51E2-ETV1 和 UBTF-ETV4 在两个 PCa 中。OR51E2 编码一种 G 蛋白偶联受体，在 PCa 中过度表达，而 UBTF 是一种广泛表达的基因，编码一种参与核糖体生物发生的 HMG 盒 DNA 结合蛋白。我们还描述了两个先前描述的基因的新基因融合组合，即 SLC45A3-ETV4 和 HERVK17-ETV4。最后，我们发现一个 PCa 中有 TMPRSS2-ETV1，一个中有 C15orf21-ETV1，一个中有 EST14-ETV1，两个中有 14q133-q21.1-ETV1。在 9 例（8 例 ETV1 和 1 例 ETV5）表现出 FISH 检测到的 ETS 异常表达和基因组重排的 PCa 中，未发现 5' 融合伙伴。我们的研究结果对描述 ETS 基因融合的异质群体有重要贡献，并表明与一种 ETS 基因描述为 5' 融合伙伴的所有基因很可能与参与前列腺癌发生的其他 ETS 基因发生重排。
