Rearranged During Transfection Rearrangement Detection by Fluorescence In Situ Hybridization Compared With Other Techniques in NSCLC

Abstract

Introduction: RET rearrangements occur in 1% to 2% NSCLCs. Since no clinically validated RET antibody is currently available, fluorescence in situ hybridization (FISH) is often used as a screening tool to identify patients likely to benefit from RET-targeted therapy. In this study, we performed a comprehensive review of publications in which RET-rearrangement testing was performed by FISH and compared the methods and results with our data. Methods: The findings of an electronic search for publications using RET-FISH in lung cancer were compared with the results obtained at the Grenoble University Hospital where 784 EGFR-, KRAS-, ALK-, and ROS1-negative NSCLCs were tested by RET break-apart FISH and confirmed by RNA-sequencing (RNA-seq). Results: Out of the 85 publications using RET-FISH analysis, 52 pertained to patients with lung cancer. The most often used positivity threshold was 15%. Six publications compared RET-FISH with at least one other molecular technique on at least eight samples, and the concordance was variable, from 5.9% to 66.7% for FISH-positive cases. Regarding our data, out of the 784 analyzed samples, 32 (4%) were positive by RET-FISH. The concordance between RET-FISH and RNA-seq in RET-FISH positive samples was 69%. Conclusions: Overall, both existing literature and our data suggest that RET-FISH testing can be used for rapid screening of RET rearrangements in NSCLC. Nevertheless, using an orthogonal technique such as RNA-seq to confirm RET-FISH-positive cases is essential for ensuring that only patients likely to benefit from RET-target therapy receive the treatment.

Keywords

• RET
• Fusion gene
• Lung cancer
• FISH
• RNA-sequencing
• Targeted therapy