Complex patterns of ETS gene alteration arise during cancer development in the human prostate

被引:112
作者
Clark, J. [1 ]
Attard, G. [1 ,2 ]
Jhavar, S. [1 ]
Flohr, P. [1 ]
Reid, A. [1 ,2 ]
De-Bono, J. [1 ,2 ]
Eeles, R. [1 ,2 ]
Scardino, P. [3 ]
Cuzick, J. [4 ]
Fisher, G. [4 ]
Parker, M. D. [1 ]
Foster, C. S. [5 ]
Berney, D. [6 ]
Kovacs, G. [7 ]
Cooper, C. S. [1 ]
机构
[1] Male Urol Canc Res Ctr, Inst Canc Res, Sutton SM2 5NG, Surrey, England
[2] Royal Marsden NHS Trust Fdn Hosp, Sutton, Surrey, England
[3] Mem Sloan Kettering Canc Ctr, Dept Urol, New York, NY 10021 USA
[4] Univ London, Wolfson Inst Prevent Med, London, England
[5] Univ Liverpool, Dept Pathol, Royal Liverpool Univ Hosp, Liverpool L69 3BX, Merseyside, England
[6] St Bartholomews Hosp, Orchid Tissue Lab, London, England
[7] Heidelberg Univ, Fac Med, Mol Oncol Lab, Heidelberg, Germany
基金
英国医学研究理事会;
关键词
prostate cancer; ERG; TMPRSS2; ERG fusion transcripts;
D O I
10.1038/sj.onc.1210843
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1993 / 2003
页数:11
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