Resumen de Multiplexed Gene Expression and Fusion Transcript Analysis to Detect ALK Fusions in Lung Cancer
Maruja E. Lira, Tae Min Kim, Donghui Huang, Shibing Deng, Youngil Koh, Bogun Jang, Heounjeong Go, Se Hoon Lee, Doo Hyun Chung, Woo Ho Kim, Eric F. P. M. Schoenmakers, Yoon La Choi, Keunchil Park, Jin Seok Ahn, Jong Mu Sun, Myung Ju Ahn, Dong Wan Kim, Mao Mao
Anaplastic lymphoma kinase gene (ALK) fusions have been identified in approximately 5% of non-small-cell lung carcinomas (NSCLCs) and define a distinct subpopulation of patients with lung cancer who are highly responsive to ALK kinase inhibitors, such as crizotinib. Because of this profound therapeutic implication, the latest National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology recommend upfront ALK screening for all patients with NSCLC. The Food and Drug Administration�approved companion diagnostic test (ie, fluorescence in situ hybridization) for identification of ALK-positive patients, however, is complex and has considerable limitations in terms of cost and throughput, making it difficult to screen many patients. To explore alternative screening modalities for detecting ALK fusions, we designed a combination of two transcript-based assays to detect for presence or absence of ALK fusions using NanoString�s nCounter technology. By using this combined gene expression and ALK fusion detection strategy, we developed a multiplexed assay with a quantitative scoring modality that is highly sensitive, reproducible, and capable of detecting low-abundant ALK fusion transcripts, even in samples with a low tumor cell content. In 66 archival NSCLC samples, our results were highly concordant to prior results obtained by fluorescence in situ hybridization and IHC. Our assay offers a cost-effective, easy-to-perform, high-throughput, and FFPE-compatible screening alternative for detection of ALK fusions.
