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人类前列腺癌中ETV1易位的异质性及临床意义

Heterogeneity and clinical significance of ETV1 translocations in human prostate cancer.

作者信息

Attard G, Clark J, Ambroisine L, Mills I G, Fisher G, Flohr P, Reid A, Edwards S, Kovacs G, Berney D, Foster C, Massie C E, Fletcher A, De Bono J S, Scardino P, Cuzick J, Cooper C S

机构信息

Institute of Cancer Research, Male Urological Cancer Research Centre, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK.

出版信息

Br J Cancer. 2008 Jul 22;99(2):314-20. doi: 10.1038/sj.bjc.6604472. Epub 2008 Jul 1.

Abstract

A fluorescence in situ hybridisation (FISH) assay has been used to screen for ETV1 gene rearrangements in a cohort of 429 prostate cancers from patients who had been diagnosed by trans-urethral resection of the prostate. The presence of ETV1 gene alterations (found in 23 cases, 5.4%) was correlated with higher Gleason Score (P=0.001), PSA level at diagnosis (P=<0.0001) and clinical stage (P=0.017) but was not linked to poorer survival. We found that the six previously characterised translocation partners of ETV1 only accounted for 34% of ETV1 re-arrangements (eight out of 23) in this series, with fusion to the androgen-repressed gene C15orf21 representing the commonest event (four out of 23). In 5'-RACE experiments on RNA extracted from formalin-fixed tissue we identified the androgen-upregulated gene ACSL3 as a new 5'-translocation partner of ETV1. These studies report a novel fusion partner for ETV1 and highlight the considerable heterogeneity of ETV1 gene rearrangements in human prostate cancer.

摘要

荧光原位杂交(FISH)检测已用于筛查429例经前列腺经尿道切除术诊断的前列腺癌患者队列中的ETV1基因重排情况。ETV1基因改变(在23例中发现,占5.4%)与更高的Gleason评分(P = 0.001)、诊断时的PSA水平(P < 0.0001)和临床分期(P = 0.017)相关,但与较差的生存率无关。我们发现,ETV1先前已鉴定的六个易位伴侣仅占该系列中ETV1重排(23例中的8例)的34%,与雄激素抑制基因C15orf21融合是最常见的事件(23例中的4例)。在从福尔马林固定组织中提取的RNA进行的5'-RACE实验中,我们鉴定出雄激素上调基因ACSL3是ETV1的一个新的5'-易位伴侣。这些研究报告了ETV1的一种新型融合伴侣,并突出了人类前列腺癌中ETV1基因重排的显著异质性。

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