Department of Laboratory Medicine and Pathobiology, University of Toronto, ON, Canada.
Anticancer Res. 2012 Sep;32(9):3629-41.
BACKGROUND/AIM: Shortcomings of current methods of prostate cancer detection call for improved biomarkers. The transmembrane protease, serine 2:ets-related gene (TMPRSS2:ERG) gene fusion leads to the overexpression of ERG, an E-twenty six (ETS) family transcription factor, and is the most prevalent genetic lesion in prostate cancer, but its clinical utility remains unclear.
Two radical prostatectomy samples were analysed by next-generation whole-transcriptome sequencing. The chosen samples differed in fusion gene status, as previously determined by reverse transcription polymerase chain reaction (RT-PCR).
Next-generation sequencing identified the involvement of novel and previously reported prostate cancer-related transcripts, the WNT signalling pathway, evasion of p53-mediated anti-proliferation and several ETS-regulated pathways in the prostate cancer cases examined. Overexpression of Rho GDP-dissociation inhibitor (RhoGDIB), a gene associated with fusion-positive prostate cancer, was found to elicit spindle-shaped morphology, faster cell migration and increased cell proliferation, phenotypic changes suggestive of cancer progression.
The present findings confirm the value of comprehensive sequencing for biomarker development and provide potential avenues of future study.
背景/目的：当前前列腺癌检测方法的不足需要改进生物标志物。跨膜丝氨酸蛋白酶 2：ETS 相关基因（TMPRSS2:ERG）基因融合导致 ERG 的过表达，ERG 是 E-二十六（ETS）家族转录因子，是前列腺癌中最常见的遗传病变，但其临床应用仍不清楚。
通过下一代全转录组测序分析了两个根治性前列腺切除术样本。所选样本的融合基因状态不同，如先前通过逆转录聚合酶链反应（RT-PCR）确定的那样。
下一代测序鉴定了涉及新的和以前报道的前列腺癌相关转录物、WNT 信号通路、逃避 p53 介导的抗增殖和几个 ETS 调节途径的前列腺癌病例。发现与融合阳性前列腺癌相关的 Rho GDP 解离抑制剂（RhoGDIB）基因的过表达可引起梭形形态、更快的细胞迁移和增加的细胞增殖，这些表型变化提示癌症进展。
本研究结果证实了全面测序在生物标志物开发中的价值，并为未来的研究提供了潜在的途径。
