ESR1 Amplification in Breast Cancer by Optimized RNase FISH: Frequent but Low-Level and Heterogeneous
ESR1 Amplification in Breast Cancer by Optimized RNase FISH: Frequent but Low-Level and Heterogeneous
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DOI：
10.1371/journal.pone.0084189
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发表时间：
2013-12-18
期刊：
影响因子：
3.7
通讯作者：
van Diest, Paul J.
中科院分区：
文献类型：
--
作者：
Moelans, Cathy B.;Holst, Frederik;van Diest, Paul J.
乳腺癌中ESR1扩增的患病率存在高度争议，差异与不同的技术方案和不同的评分方法有关。此外，有人提出mrna前伪影会影响ESR1 FISH分析的结果。我们结合改进的RNase FISH协议和多重连接依赖探针扩增（MLPA）分析了激光显微解剖后ESR1基因拷贝数状态。FISH显示，尽管使用RNase治疗，但ESR1增益和扩增的发生率很高，但MLPA未证实FISH在超过一半的病例中检测到ESR1拷贝数增加。我们认为，esr1特异性肿瘤内异质性和低水平拷贝数增加的结合解释了这些差异。
Prevalence of ESR1 amplification in breast cancer is highly disputed and discrepancies have been related to different technical protocols and different scoring approaches. In addition, pre-mRNA artifacts have been proposed to influence outcome of ESR1 FISH analysis. We analyzed ESR1 gene copy number status combining an improved RNase FISH protocol with multiplex ligation-dependent probe amplification (MLPA) after laser microdissection. FISH showed a high prevalence of ESR1 gains and amplifications despite RNase treatment but MLPA did not confirm ESR1 copy number increases detected by FISH in more than half of cases. We suggest that the combination of the ESR1-specific intra-tumor heterogeneity and low-level copy number increase accounts for these discrepancies.