Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA.
Mod Pathol. 2010 Apr;23(4):539-46. doi: 10.1038/modpathol.2009.193. Epub 2010 Jan 29.
The majority of prostate cancers harbor recurrent gene fusions between the hormone-regulated TMPRSS2 and members of the ETS family of transcription factors, most commonly ERG. Prostate cancer with ERG rearrangements represent a distinct sub-class of tumor based on studies reporting associations with histomorphologic features, characteristic somatic copy number alterations, and gene expression signatures. This study describes the frequency of ERG rearrangement prostate cancer and three 5 prime (5') gene fusion partners (ie, TMPRSS2, SLC45A3, and NDRG1) in a large prostatectomy cohort. ERG gene rearrangements and mechanism of rearrangement, as well as rearrangements of TMPRSS2, SLC45A3, and NDRG1, were assessed using fluorescence in situ hybridization (FISH) on prostate cancer samples from 614 patients treated using radical prostatectomy. ERG rearrangement occurred in 53% of the 540 assessable cases. TMPRSS2 and SLC45A3 were the only 5' partner in 78% and 6% of these ERG rearranged cases, respectively. Interestingly, 11% of the ERG rearranged cases showed concurrent TMPRSS2 and SLC45A3 rearrangements. TMPRSS2 or SLC45A3 rearrangements could not be identified for 5% of the ERG rearranged cases. From these remaining cases we identified one case with NDRG1 rearrangement. We did not observe any associations with pathologic parameters or clinical outcome. This is the first study to describe the frequency of SLC45A3-ERG fusions in a large clinical cohort. Most studies have assumed that all ERG rearranged prostate cancers harbor TMPRSS2-ERG fusions. This is also the first study to report concurrent TMPRSS2 and SLC45A3 rearrangements in the same tumor focus, suggesting additional complexity that had not been previously appreciated. This study has important clinical implications for the development of diagnostic assays to detect ETS rearranged prostate cancer. Incorporation of these less common ERG rearranged prostate cancer fusion assays could further increase the sensitivity of the current PCR-based approaches.
大多数前列腺癌都存在激素调节的 TMPRSS2 与 ETS 家族转录因子成员之间的复发性基因融合，最常见的是 ERG。基于研究报告与组织形态学特征、特征性体细胞拷贝数改变和基因表达特征相关联，具有 ERG 重排的前列腺癌代表了一种独特的肿瘤亚类。本研究描述了在一个大型前列腺切除术队列中 ERG 重排前列腺癌和三个 5' 基因融合伙伴（即 TMPRSS2、SLC45A3 和 NDRG1）的频率。使用荧光原位杂交（FISH）评估 614 例接受根治性前列腺切除术治疗的前列腺癌样本中的 ERG 基因重排和重排机制，以及 TMPRSS2、SLC45A3 和 NDRG1 的重排。在 540 例可评估病例中，有 53%的病例发生 ERG 重排。在这些 ERG 重排病例中，TMPRSS2 和 SLC45A3 分别是唯一的 5' 伙伴，分别占 78%和 6%。有趣的是，11%的 ERG 重排病例同时存在 TMPRSS2 和 SLC45A3 重排。对于 5%的 ERG 重排病例，无法确定 TMPRSS2 或 SLC45A3 重排。在这些剩余病例中，我们发现了一例 NDRG1 重排病例。我们没有观察到任何与病理参数或临床结果相关的关联。这是第一项描述 SLC45A3-ERG 融合在大型临床队列中的频率的研究。大多数研究都假设所有 ERG 重排的前列腺癌都存在 TMPRSS2-ERG 融合。这也是第一项报告在同一肿瘤焦点中同时存在 TMPRSS2 和 SLC45A3 重排的研究，表明存在以前未被认识到的额外复杂性。这项研究对开发用于检测 ETS 重排前列腺癌的诊断检测具有重要的临床意义。纳入这些不太常见的 ERG 重排前列腺癌融合检测可以进一步提高当前基于 PCR 的方法的敏感性。
