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A Single-Tube Multiplexed Assay for Detecting ALK, ROS1,and RETFusions in Lung Cancer
- Source :
- The Journal of Molecular Diagnostics; March 2014, Vol. 16 Issue: 2 p229-243, 15p
- Publication Year :
- 2014
-
Abstract
- Approximately 7% of non–small cell lung carcinomas (NSCLCs) harbor oncogenic fusions involving ALK, ROS1, and RET. Although tumors harboring ALKfusions are highly sensitive to crizotinib, emerging preclinical and clinical data demonstrate that patients with ROS1or RETfusions may also benefit from inhibitors targeting these kinases. Using a transcript-based method, we designed a combination of 3′ overexpression and fusion-specific detection strategies to detect ALK, ROS1 and RET fusion transcripts in NSCLC tumors. We validated the assay in 295 NSCLC specimens and showed that the assay is highly sensitive and specific. ALKresults were 100% concordant with fluorescence in situhybridization (FISH) (n= 52) and 97.8% concordant with IHC (n= 179) [sensitivity, 96.8% (95% CI 91.0%–98.9%); specificity, 98.8% (95% CI 93.6%–99.8%)]. For ROS1and RET, we also observed 100% concordance with FISH (n= 46 and n= 15, respectively). We identified seven ROS1and 14 RETfusion–positive tumors and confirmed the fusion status by RT-PCR and FISH. One RETfusion involved a novel partner, cutlike homeobox 1 gene (CUX1), yielding an in-frame CUX1-RET fusion. ROS1and RETfusions were significantly enriched in tumors without KRAS/EGFR/ALKalterations. ALK/ROS1/RET/EGFR/KRASalterations were mutually exclusive. As a single-tube assay, this test shows promise as a more practical and cost-effective screening modality for detecting rare but targetable fusions in NSCLC.
Details
- Language :
- English
- ISSN :
- 15251578
- Volume :
- 16
- Issue :
- 2
- Database :
- Supplemental Index
- Journal :
- The Journal of Molecular Diagnostics
- Publication Type :
- Periodical
- Accession number :
- ejs32131185
- Full Text :
- https://doi.org/10.1016/j.jmoldx.2013.11.007