Laxman Bharathi, Tomlins Scott A, Mehra Rohit, Morris David S, Wang Lei, Helgeson Beth E, Shah Rajal B, Rubin Mark A, Wei John T, Chinnaiyan Arul M
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Neoplasia. 2006 Oct;8(10):885-8. doi: 10.1593/neo.06625.
We recently reported the identification of recurrent gene fusions in the majority of prostate cancers involving the 5' untranslated region of the androgen-regulated gene TMPRSS2 and the ETS family members ERG, ETV1, and ETV4. Here we report the noninvasive detection of these gene fusions in the urine of patients with clinically localized prostate cancer. By quantitative polymerase chain reaction, we assessed the expression of ERG and TMPRSS2:ERG transcripts in urine samples obtained after prostatic massage from 19 patients (11 prebiopsy and 8 pre-radical prostatectomy) with prostate cancer. We observed a strong concordance between ERG overexpression and TMPRSS2:ERG expression, with 8 of 19 (42%) patients having detectable TMPRSS2:ERG transcripts in their urine. Importantly, by fluorescence in situ hybridization, we confirmed the presence or the absence of TMPRSS2:ERG gene fusions in matched prostate cancer tissue samples from three of three patients with fusion transcripts in their urine and from two of two patients without fusion transcripts in their urine. These results demonstrate that TMPRSS2:ERG gene fusions can be detected in the urine of patients with prostate cancer and support larger studies on prospective cohorts for noninvasive detection of prostate cancer.
我们最近报告称，在大多数前列腺癌中发现了复发性基因融合，这些融合涉及雄激素调节基因TMPRSS2的5'非翻译区以及ETS家族成员ERG、ETV1和ETV4。在此，我们报告了在临床局限性前列腺癌患者尿液中对这些基因融合的非侵入性检测。通过定量聚合酶链反应，我们评估了19例前列腺癌患者（11例活检前和8例根治性前列腺切除术前）前列腺按摩后获得的尿液样本中ERG和TMPRSS2:ERG转录本的表达。我们观察到ERG过表达与TMPRSS2:ERG表达之间有很强的一致性，19例患者中有8例（42%）尿液中可检测到TMPRSS2:ERG转录本。重要的是，通过荧光原位杂交，我们在尿液中有融合转录本的3例患者中的3例以及尿液中无融合转录本的2例患者中的2例的匹配前列腺癌组织样本中证实了TMPRSS2:ERG基因融合的存在或不存在。这些结果表明，前列腺癌患者尿液中可检测到TMPRSS2:ERG基因融合，并支持对前列腺癌非侵入性检测的前瞻性队列进行更大规模的研究。
