文章：

前列腺癌复发性基因融合

Recurrent gene fusions in prostate cancer

原文发布日期：2008-06-19

DOI: 10.1038/nrc2402

类型: Review Article

开放获取: 否

要点：

1. Approximately 50% of prostate cancers from serum prostate-specific antigen (PSA)-screened cohorts harbour recurrent gene fusions.
2. The gene fusions in prostate cancer are characterized by 5′ genomic regulatory elements, most commonly controlled by androgen, fused to members of the Ets family of transcription factors.
3. TMPRSS2–ERG is the most common gene fusion, present in about half of all localized prostate cancers analysed. TMPRSS2 also fuses to other Ets family genes such as ETV1, ETV4 and ETV5 in a small percentage of prostate cancers.
4. ETV1, ETV4 and ETV5 have additional 5′ fusion partners that differ in their prostate specificity and response to androgen.
5. Many Ets gene fusion transcript variants have been identified with different 5′ and 3′ partner sequences, probably with prognostic and/or diagnostic implications.
6. Prostate cancers harbouring TMPRSS2–ERG gene fusion display characteristic morphological features of prostate cancers, such as macronucleoli and intraductal tumour spread as well as rare blue-tinged mucin, cribriform growth pattern and signet-ring cell.
7. ERG overexpression imparts invasiveness to prostate cells in vitro and induces plasminogen activation and matrix metalloproteinase pathways.
8. Ets gene fusion-positive and Ets gene fusion-negative prostate cancers have distinct chromosomal aberrations, expression signatures, morphological features and clinical outcomes, suggesting that they are fundamentally different classes of prostate cancer.
9. Sensitive and specific diagnostic tests and targeted therapeutics will affect the detection and management of Ets-positive prostate cancer.

要点翻译：

1. 在经血清前列腺特异性抗原（PSA）筛查队列中，约50%的前列腺癌存在复发性基因融合现象。
2. 前列腺癌中的基因融合特征表现为：5′端基因组调控元件（最常见受雄激素调控）与Ets转录因子家族成员发生融合。
3. TMPRSS2-ERG是最常见的基因融合类型，存在于约半数已分析的局限性前列腺癌中。TMPRSS2亦可与Ets家族其他基因（如ETV1、ETV4和ETV5）发生融合，但仅见于少数前列腺癌病例。
4. ETV1、ETV4和ETV5还存在其他5′端融合伴侣，这些伴侣基因在前列腺特异性及雄激素应答方面存在差异。
5. 目前已在Ets基因融合转录本中发现多种变异型，其5′和3′端伴侣序列各不相同，这可能具有预后和/或诊断意义。
6. 携带TMPRSS2-ERG基因融合的前列腺癌呈现特征性形态学表现，包括巨核仁、导管内肿瘤播散、罕见蓝色黏液、筛状生长模式及印戒细胞等。
7. 体外实验表明，ERG过表达可增强前列腺细胞的侵袭能力，并激活纤溶酶原及基质金属蛋白酶通路。
8. Ets基因融合阳性与阴性前列腺癌在染色体畸变、表达谱、形态学特征及临床结局方面均存在显著差异，提示二者本质属于不同亚型的前列腺癌。
9. 开发高灵敏度、高特异性的诊断检测方法及靶向治疗策略，将对Ets阳性前列腺癌的检出与临床管理产生重要影响。

英文摘要：

The discovery of recurrent gene fusions in a majority of prostate cancers has important clinical and biological implications in the study of common epithelial tumours. Gene fusion and chromosomal rearrangements were previously thought to be primarily the oncogenic mechanism of haematological malignancies and sarcomas. The prostate cancer gene fusions that have been identified thus far are characterized by 5′ genomic regulatory elements, most commonly controlled by androgen, fused to members of the Ets family of transcription factors, leading to the overexpression of oncogenic transcription factors. Ets gene fusions probably define a distinct class of prostate cancer, and this might have a bearing on diagnosis, prognosis and rational therapeutic targeting.

摘要翻译： 

在大多数前列腺癌中发现复发性基因融合，对常见上皮性肿瘤的研究具有重要的临床和生物学意义。此前，人们认为基因融合和染色体重排主要是血液系统恶性肿瘤和肉瘤的致癌机制。目前已发现的前列腺癌基因融合，其特征是由5′端基因组调控元件（最常见的是受雄激素调控）与Ets转录因子家族成员融合，导致致癌转录因子的过表达。Ets基因融合可能界定了前列腺癌的一个独特亚型，这可能对诊断、预后以及合理的靶向治疗产生影响。

原文链接：

Recurrent gene fusions in prostate cancer