Complex patterns of ETS gene alteration arise during cancer development in the human prostate
Complex patterns of ETS gene alteration arise during cancer development in the human prostate
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DOI：
10.1038/sj.onc.1210843
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发表时间：
2008-03-27
期刊：
影响因子：
8
通讯作者：
Cooper, C. S.
中科院分区：
文献类型：
--
作者：
Clark, J.;Attard, G.;Cooper, C. S.
ERG基因“分离”荧光原位杂交(FISH)技术已被用于筛选完整的前列腺癌切除标本的ERG基因重排。在含有ERG改变的癌症中，观察到的改变模式通常是复杂的。在同一前列腺癌切片中，不同类型的ERG基因改变可以同时发生在同一癌变区域，也可以发生在不同的癌灶中。在某些情况下，ERG改变的特殊模式的并列提示了肿瘤进展的可能机制。携带ERG改变的前列腺癌通常也含有缺乏ERG基因重排的癌症。一次经尿道切除的前列腺标本同时含有ERG和ETV1基因重排，这表明所观察到的复杂性至少部分可以由单个前列腺中独立出现的多个ETS基因改变来解释。为了寻找可能的前体病变，在高级别前列腺上皮内瘤变(PIN)和与低级别PIN诊断一致的非典型原位上皮病变中都发现了克隆性ERG重排。我们的观察结果支持这样的观点，即ERG基因的改变代表了一种启动事件，它最初促进了克隆性扩张，形成了上皮非典型性区域。在前列腺癌切除标本中发现的ERG改变的复杂模式对于研究个体前列腺癌的临床意义和发生机制的实验设计具有重要的意义。
An ERG gene 'break-apart' fluorescence in situ hybridization (FISH) assay has been used to screen whole-mount prostatectomy specimens for rearrangements at the ERG locus. In cancers containing ERG alterations the observed pattern of changes was often complex. Different categories of ERG gene alteration were found either together in a single cancerous region or within separate foci of cancer in the same prostate slice. In some cases the juxtaposition of particular patterns of ERG alterations suggested possible mechanisms of tumour progression. Prostates harbouring ERG alterations commonly also contained cancer that lacked rearrangements of the ERG gene. A single trans-urethral resection of the prostate specimen examined harboured both ERG and ETV1 gene rearrangements demonstrating that the observed complexity may, at least in part, be explained by multiple ETS gene alterations arising independently in a single prostate. In a search for possible precursor lesions clonal ERG rearrangements were found both in high grade prostatic intraepithelial neoplasia (PIN) and in atypical in situ epithelial lesions consistent with the diagnosis of low grade PIN. Our observations support the view that ERG gene alterations represent an initiating event that promotes clonal expansion initially to form regions of epithelial atypia. The complex patterns of ERG alteration found in prostatectomy specimens have important implications for the design of experiments investigating the clinical significance and mechanism of development of individual prostate cancers.