Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Oncology Research, Pfizer, San Diego, California, USA.
Sci Rep. 2017 Feb 9;7:42259. doi: 10.1038/srep42259.
ALK, ROS1 and RET gene fusions are important predictive biomarkers for tyrosine kinase inhibitors in lung cancer. Currently, the gold standard method for gene fusion detection is Fluorescence In Situ Hybridization (FISH) and while highly sensitive and specific, it is also labour intensive, subjective in analysis, and unable to screen a large numbers of gene fusions. Recent developments in high-throughput transcriptome-based methods may provide a suitable alternative to FISH as they are compatible with multiplexing and diagnostic workflows. However, the concordance between these different methods compared with FISH has not been evaluated. In this study we compared the results from three transcriptome-based platforms (Nanostring Elements, Agena LungFusion panel and ThermoFisher NGS fusion panel) to those obtained from ALK, ROS1 and RET FISH on 51 clinical specimens. Overall agreement of results ranged from 86-96% depending on the platform used. While all platforms were highly sensitive, both the Agena panel and Thermo Fisher NGS fusion panel reported minor fusions that were not detectable by FISH. Our proof-of-principle study illustrates that transcriptome-based analyses are sensitive and robust methods for detecting actionable gene fusions in lung cancer and could provide a robust alternative to FISH testing in the diagnostic setting.
ALK、ROS1 和 RET 基因融合是肺癌酪氨酸激酶抑制剂的重要预测生物标志物。目前，基因融合检测的金标准方法是荧光原位杂交（FISH），虽然它高度敏感和特异，但也很耗费人力，分析具有主观性，并且无法筛选大量的基因融合。基于高通量转录组的方法的最新进展可能为 FISH 提供一种合适的替代方法，因为它们与多重和诊断工作流程兼容。然而，这些不同方法与 FISH 之间的一致性尚未得到评估。在这项研究中，我们比较了三种基于转录组的平台（Nanostring Elements、Agena LungFusion 试剂盒和 ThermoFisher NGS 融合试剂盒）与 ALK、ROS1 和 RET FISH 在 51 个临床标本上的结果。根据所使用的平台，结果的总体一致性从 86%到 96%不等。虽然所有平台都具有高度敏感性，但 Agena 试剂盒和 Thermo Fisher NGS 融合试剂盒都报告了微小融合，这些融合无法通过 FISH 检测到。我们的原理验证研究表明，基于转录组的分析是检测肺癌中可操作基因融合的敏感和强大方法，并且可以为诊断环境中的 FISH 测试提供强大的替代方法。
