Rajput Ashish B, Miller Melinda A, De Luca Alessandro, Boyd Niki, Leung Sam, Hurtado-Coll Antonio, Fazli Ladan, Jones Edward C, Palmer Jodie B, Gleave Martin E, Cox Michael E, Huntsman David G
Genetic Pathology Evaluation Centre, Vancouver General Hospital, British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada.
J Clin Pathol. 2007 Nov;60(11):1238-43. doi: 10.1136/jcp.2006.043810. Epub 2007 Jan 26.
Recent reports indicate that prostate cancers (CaP) frequently over-express the potential oncogenes, ERG or ETV1. Many cases have chromosomal rearrangements leading to the fusion of the 5' end of the androgen-regulated serine protease TMPRSS2 (21q22.2) to the 3' end of either ERG (21q22.3) or ETV1 (7p21.3). The consequence of these rearrangements is aberrant androgen receptor-driven expression of the potential oncogenes, ETV1 or ERG.
To determine the frequency of rearrangements involving TMPRSS2, ERG, or ETV1 genes in CaP of varying Gleason grades through fluorescence in situ hybridisation (FISH) on CaP tissue microarrays (TMAs).
Two independent assays, a TMPRSS2 break-apart assay and a three-colour gene fusion FISH assay were applied to TMAs. FISH positive cases were confirmed by reverse transcriptase (RT) PCR and DNA sequence analysis.
A total of 106/196 (54.1%) cases were analysed by FISH. None of the five benign prostatic hyperplasia cases analysed exhibited these gene rearrangements. TMPRSS2:ERG fusion was found more frequently in moderate to poorly differentiated tumours (35/86, 40.7%) than in well differentiated tumours (1/15, 6.7%, p = 0.017). TMPRSS2:ETV1 gene fusions were not detected in any of the cases tested. TMPRSS2:ERG fusion product was verified by RT-PCR followed by DNA sequencing in 7/7 randomly selected positive cases analysed.
This study indicates that TMPRSS2:ERG gene rearrangements in CaP may be used as a diagnostic tool to identify prognostically relevant sub-classifications of these cancers.
近期报告显示，前列腺癌（CaP）常常过度表达潜在致癌基因ERG或ETV1。许多病例存在染色体重排，导致雄激素调节的丝氨酸蛋白酶TMPRSS2（21q22.2）的5'端与ERG（21q22.3）或ETV1（7p21.3）的3'端融合。这些重排的结果是潜在致癌基因ETV1或ERG受雄激素受体驱动异常表达。
通过对CaP组织微阵列（TMA）进行荧光原位杂交（FISH），确定不同Gleason分级的CaP中涉及TMPRSS2、ERG或ETV1基因重排的频率。
对TMA应用两种独立检测方法，即TMPRSS2断裂分析和三色基因融合FISH检测。FISH阳性病例通过逆转录酶（RT）PCR和DNA序列分析进行确认。
共对106/196（54.1%）例进行了FISH分析。所分析的5例良性前列腺增生病例均未出现这些基因重排。TMPRSS2:ERG融合在中分化至低分化肿瘤（35/86，40.7%）中比高分化肿瘤（1/15，6.7%，p = 0.017）中更常见。在所检测的任何病例中均未检测到TMPRSS2:ETV1基因融合。在随机选择的7/7例分析的阳性病例中，通过RT-PCR随后进行DNA测序验证了TMPRSS2:ERG融合产物。
本研究表明，CaP中的TMPRSS2:ERG基因重排可作为一种诊断工具，用于识别这些癌症预后相关的亚分类。
