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Multiplexed Gene Expression and Fusion Transcript Analysis to Detect ALK Fusions in Lung Cancer

Cited 48 time in Web of Science Cited 50 time in Scopus
Authors
Lira, Maruja E.; Kim, Tae Min; Huang, Donghui; Deng, Shibing; Koh, Youngil; Jang, Bogun; Go, Heounjeong; Lee, Se-Hoon; Chung, Doo Hyun; Kim, Woo-Ho; Schoenmakers, Eric F. P. M.; Choi, Yoon-La; Park, Keunchil; Ahn, Jin Seok; Sun, Jong-Mu; Ahn, Myung-Ju; Kim, Dong-Wan; Mao, Mao
Issue Date
2013-01
Citation
Journal of Molecular Diagnostics, Vol.15 No.1, pp.51-61
Abstract
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. (J Mol Diagn 2013, 15: 51-61; http://dx.doi.org/10.1016/j.jmoldx.2012.08.006)
ISSN
1525-1578
URI
https://hdl.handle.net/10371/165476
DOI
https://doi.org/10.1016/j.jmoldx.2012.08.006
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
College of Medicine/School of Medicine (의과대학/대학원)Cancer Research Institute (암연구소)Journal Papers (저널논문_암연구소)
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