TMPRSS2-ERG gene fusion is not associated with outcome in patients treated by prostatectomy.
TMPRSS2-ERG gene fusion is not associated with outcome in patients treated by prostatectomy.
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DOI：
10.1158/0008-5472.can-08-2467
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发表时间：
2009-02-15
期刊：
影响因子：
11.2
通讯作者：
Gerald WL
中科院分区：
文献类型：
--
作者：
Gopalan A;Leversha MA;Satagopan JM;Zhou Q;Al-Ahmadie HA;Fine SW;Eastham JA;Scardino PT;Scher HI;Tickoo SK;Reuter VE;Gerald WL
大量前列腺癌已显示具有复发性染色体重排，导致雄激素调节的TMPRSS 2启动子融合至ETS转录因子家族的成员，最常见的是ERG。这导致ERG过表达，其可能在前列腺肿瘤发生或进展中具有直接因果作用。然而，重排的临床意义尚不清楚，特别是，在最近的报告中与结局的关系不一致。我们通过荧光原位杂交（FISH）分析了521例临床定位手术治疗的前列腺癌患者的TMPRSS 2-ERG基因重排状态，中位随访时间为95个月，并在40例不匹配的转移瘤中进行了分析。42%的原发肿瘤和40%的转移瘤有重排。11%有TMPRRS 2-ERG区域的拷贝数增加（CNI）。重排单独与低级别相关，但与分期、生化复发、转移或死亡无关。CNI伴和不伴重排与高级别和晚期相关。此外，具有CNI和缺失重排的癌症亚组，具有两个或更多个缺失基因座的拷贝，倾向于更具临床侵袭性。DNA指数评估显示，大多数具有TMPRSS 2-ERG CNI的肿瘤具有广泛的非整倍体/四倍体，而不具有TMPRSS 2-ERG CNI的肿瘤主要是二倍体。因此，我们得出结论，TMPRSS 2-ERG易位与结果无关，与21号染色体CNI相关的侵袭性临床特征反映了广泛的非整倍体，而不是由于CNI特异性重排TMPRSS 2-ERG。
A significant number of prostate cancers have been shown to have recurrent chromosomal rearrangements resulting in the fusion of the androgen regulated TMPRSS2 promoter to a member of the ETS transcription factor family, most commonly ERG. This results in ERG overexpression which may have a direct causal role in prostate tumorigenesis or progression. However, the clinical significance of the rearrangement is unclear and, in particular, relationship to outcome has been inconsistent in recent reports. We analyzed TMPRSS2-ERG gene rearrangement status by fluorescence in situ hybridization (FISH) in 521 cases of clinically localized surgically treated prostate cancer with 95 months median follow-up and also in 40 unmatched metastases. 42% of primary tumors and 40% of metastases had rearrangements. 11% had copy number increase (CNI) of the TMPRRS2-ERG region. Rearrangement alone was associated with lower grade, but not with stage, biochemical recurrence, metastases or death. CNI with and without rearrangement was associated with high grade and advanced stage. Further, a subgroup of cancers with CNI and rearrangement by deletion, with two or more copies of the deleted locus, tended to be more clinically aggressive. DNA index assessment revealed that the majority of tumors with CNI of TMPRSS2-ERG had generalized aneuploidy/ tetraploidy in contrast to tumors without TMPRSS2-ERG CNI, which were predominantly diploid. We therefore conclude that translocation of TMPRSS2-ERG is not associated with outcome and the aggressive clinical features associated with CNI of chromosome 21 reflect generalized aneuploidy and are not due to CNI specifically of rearranged TMPRSS2-ERG.