Gene fusions between TMPRSS2 and ETS family genes in prostate cancer:: frequency and transcript variant analysis by RT-PCR and FISH on paraffin-embedded tissues
Gene fusions between TMPRSS2 and ETS family genes in prostate cancer:: frequency and transcript variant analysis by RT-PCR and FISH on paraffin-embedded tissues
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DOI：
10.1038/modpathol.3800903
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发表时间：
2007-09-01
期刊：
影响因子：
7.5
通讯作者：
Chen, Yao-Tseng
中科院分区：
文献类型：
--
作者：
Tu, Jiangling J.;Rohan, Stephen;Chen, Yao-Tseng
TMPRSS2和ETS家族基因之间的复发性基因融合最近被证明在前列腺癌中发生的频率很高。在本研究中，我们使用福尔马林固定石蜡包埋组织，通过逆转录聚合酶链反应（RT-PCR）和荧光原位杂交（FISH）评估TMPRSS2-ERG和TMPRSS2-ETV1融合。结果与下游ERG和ETV1序列的过表达有关。在检查的82例病例中，通过FISH仅发现一例TMPRSS2-ETV1融合。相比之下，35例（43%）患者通过RT-PCR或FISH检测到TMPRSS2-ERG融合。缺失，而不是易位，被发现是TMPRSS2-ERG基因融合的主要机制（81%对19%）。RTPCR与FISH结果相关性较好，大多数阳性病例导致下游ERG序列过表达。几个TMPRSS2-ERG融合转录物变异被鉴定出来，其中大多数被预测编码截断的ERG蛋白。Gleason评分为6分或7分的前列腺癌TMPRSS2-ERG融合频率高于分级较高的肿瘤，但差异无统计学意义（P= 0.42）。另一方面，与黏液蛋白阴性的肿瘤相比，黏液蛋白阳性的肿瘤更常包含这样的基因融合（P = 0.004）。这些形态学上的相关性，更重要的是这种融合与临床结果和治疗反应的潜在相关性，应该进一步探讨。
Recurrent gene fusions between TMPRSS2 and ETS family genes have recently been shown to occur at a high frequency in prostate cancer. In this study, we used formalin-fixed paraffin-embedded tissue and evaluated both TMPRSS2-ERG and TMPRSS2-ETV1 fusions by reverse transcription polymerase chain reaction ( RT-PCR) and fluorescence in situ hybridization ( FISH). The results were correlated to overexpression of the downstream ERG and ETV1 sequences. Of 82 cases examined, TMPRSS2-ETV1 fusion was seen in only one case, by FISH. In comparison, TMPRSS2-ERG fusion was documented in 35 cases ( 43%) by either RT-PCR or FISH. Deletion, rather than translocation, was found to be the main mechanism for TMPRSS2-ERG gene fusion ( 81 vs 19%). RTPCR and FISH results correlated well, with most positive cases resulting in overexpression of downstream ERG sequences. Several TMPRSS2-ERG fusion transcript variants were identified, most of which are predicted to encode truncated ERG proteins. Prostate cancer of Gleason's scores 6 or 7 had more frequent TMPRSS2-ERG fusions than higher-grade tumors, but this difference was not statistically significant ( P= 0.42). On the other hand, mucin-positive carcinomas more often harbor such gene fusions when compared to mucin-negative tumors ( P = 0.004). These morphological correlates, and more importantly the potential correlation of such fusions to clinical outcome and treatment responses, should be further explored.