{"title":"Rearranged During Transfection Rearrangement Detection by Fluorescence In Situ Hybridization Compared With Other Techniques in NSCLC","authors":"Anne Mc Leer PhD , Julie Mondet PharmD, PhD , Nelly Magnat MSc , Mailys Mersch MSc , Diane Giovannini MD , Camille Emprou MD , Anne-Claire Toffart MD, PhD , Nathalie Sturm MD, PhD , Sylvie Lantuéjoul MD, PhD , David Benito PhD","doi":"10.1016/j.jtocrr.2024.100714","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><div><em>RET</em> 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 <em>RET</em>-rearrangement testing was performed by FISH and compared the methods and results with our data.</div></div><div><h3>Methods</h3><div>The findings of an electronic search for publications using <em>RET</em>-FISH in lung cancer were compared with the results obtained at the Grenoble University Hospital where 784 <em>EGFR</em><em>-</em>, <em>KRAS</em><em>-</em>, <em>ALK</em>-, and <em>ROS1</em>-negative NSCLCs were tested by <em>RET</em> break-apart FISH and confirmed by RNA-sequencing (RNA-seq).</div></div><div><h3>Results</h3><div>Out of the 85 publications using <em>RET</em>-FISH analysis, 52 pertained to patients with lung cancer. The most often used positivity threshold was 15%. Six publications compared <em>RET</em>-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 <em>RET</em>-FISH. The concordance between <em>RET</em>-FISH and RNA-seq in <em>RET</em>-FISH positive samples was 69%.</div></div><div><h3>Conclusions</h3><div>Overall, both existing literature and our data suggest that <em>RET</em>-FISH testing can be used for rapid screening of <em>RET</em> rearrangements in NSCLC. Nevertheless, using an orthogonal technique such as RNA-seq to confirm <em>RET</em>-FISH-positive cases is essential for ensuring that only patients likely to benefit from <em>RET</em>-target therapy receive the treatment.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 12","pages":"Article 100714"},"PeriodicalIF":3.0000,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JTO Clinical and Research Reports","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2666364324000845","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
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.