Molecular profiling of ETS and non-ETS aberrations in prostate cancer patients from northern India.
Molecular profiling of ETS and non-ETS aberrations in prostate cancer patients from northern India.
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DOI：
10.1002/pros.22989
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发表时间：
2015-07-01
期刊：
影响因子：
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通讯作者：
Palanisamy N
中科院分区：
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作者：
Ateeq B;Kunju LP;Carskadon SL;Pandey SK;Singh G;Pradeep I;Tandon V;Singhai A;Goel A;Amit S;Agarwal A;Dinda AK;Seth A;Tsodikov A;Chinnaiyan AM;Palanisamy N
基于遗传畸变（包括ETS或RAF基因重排、PTEN缺失和SPINK1过表达）的前列腺癌（PCa）分子分层显示出明确的预后和诊断价值。涉及ETS转录因子的基因重排是PCa中常见的发病躯体事件。ETS重排在高加索PCa患者中的发生率已有报道，然而，在印度人群中的发生率在很大程度上是未知的。本研究的目的是确定该队列中ETS和RAF激酶基因重排、SPINK1过表达和PTEN缺失的患病率。在这项多中心研究中，福尔马林固定石蜡包埋（FFPE） PCa标本（n = 121）从印度的四家主要医疗机构采购。组织切片并使用免疫组织化学（IHC）、RNA原位杂交（RNA - ISH）和/或荧光原位杂交（FISH）进行分子谱分析。IHC检测到48.9% (46/94)PCa标本中ERG过表达，FISH也证实了这一点。在其他ETS家族成员中，虽然通过RNA - ISH检测到一例ETV1转录本，但未观察到ETV4的改变。SPINK1过表达占12.5% (12/96)，PTEN缺失占21.52%（17/79）。有趣的是，30%的ERG阳性病例中发现PTEN缺失（P = 0.017），而只有1例SPINK1过表达（P = 0.67）。分别在1%和4.5%的PCa病例中检测到BRAF和RAF1基因重排。这是第一个全面的分子谱分析的主要频谱的因果畸变在印度男性PCa的报告。我们的研究结果表明，北印度人群的ETS基因重排和SPINK1过表达模式与高加索人群相似，但与日本和中国的PCa患者不同。本研究中提供的分子谱数据可以帮助临床决策进行手术，诊断和治疗干预的选择。中华医学杂志，2015。©2015作者。《前列腺》，Wiley期刊公司出版。
Molecular stratification of prostate cancer (PCa) based on genetic aberrations including ETS or RAF gene‐rearrangements, PTEN deletion, and SPINK1 over‐expression show clear prognostic and diagnostic utility. Gene rearrangements involving ETS transcription factors are frequent pathogenetic somatic events observed in PCa. Incidence of ETS rearrangements in Caucasian PCa patients has been reported, however, occurrence in Indian population is largely unknown. The aim of this study was to determine the prevalence of the ETS and RAF kinase gene rearrangements, SPINK1 over‐expression, and PTEN deletion in this cohort. In this multi‐center study, formalin‐fixed paraffin embedded (FFPE) PCa specimens (n = 121) were procured from four major medical institutions in India. The tissues were sectioned and molecular profiling was done using immunohistochemistry (IHC), RNA in situ hybridization (RNA‐ISH) and/or fluorescence in situ hybridization (FISH). ERG over‐expression was detected in 48.9% (46/94) PCa specimens by IHC, which was confirmed in a subset of cases by FISH. Among other ETS family members, while ETV1 transcript was detected in one case by RNA‐ISH, no alteration in ETV4 was observed. SPINK1 over‐expression was observed in 12.5% (12/96) and PTEN deletion in 21.52% (17/79) of the total PCa cases. Interestingly, PTEN deletion was found in 30% of the ERG‐positive cases (P = 0.017) but in only one case with SPINK1 over‐expression (P = 0.67). BRAF and RAF1 gene rearrangements were detected in ∼1% and ∼4.5% of the PCa cases, respectively. This is the first report on comprehensive molecular profiling of the major spectrum of the causal aberrations in Indian men with PCa. Our findings suggest that ETS gene rearrangement and SPINK1 over‐expression patterns in North Indian population largely resembled those observed in Caucasian population but differed from Japanese and Chinese PCa patients. The molecular profiling data presented in this study could help in clinical decision‐making for the pursuit of surgery, diagnosis, and in selection of therapeutic intervention. Prostate 75:1051–1062, 2015. © 2015 The Authors. The Prostate, published by Wiley Periodicals, Inc.