Multiplexed transcriptome analysis to detect ALK, ROS1 and RET rearrangements in lung cancer

作者：Rogers Toni Maree; Arnau Gisela Mir; Ryland Georgina L; Huang Stephen; Lira Maruja E; Emmanuel Yvette; Perez Omar D; Irwin Darryl; Fellowes Andrew P; Wong Stephen Q; Fox Stephen B

来源：Scientific Reports, 2017, 7(1): 42259.

DOI：10.1038/srep42259

<jats:title>Abstract</jats:title><jats:p><jats:italic>ALK, ROS1</jats:italic> and <jats:italic>RET</jats:italic> gene fusions are important predictive biomarkers for tyrosine kinase inhibitors in lung cancer. Currently, the gold standard method for gene fusion detection is Fluorescence <jats:italic>In Situ</jats:italic> 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 <jats:italic>ALK, ROS1</jats:italic> and <jats:italic>RET</jats:italic> 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.</jats:p>

• 出版日期2017-2-9