RET Fluorescence In Situ Hybridization Analysis Is a Sensitive but Highly Unspecific Screening Method for RET Fusions in Lung Cancer

IntroductionRET gene fusions are established oncogenic drivers in 1% of NSCLC. Accurate detection advanced patients with RET is essential to ensure optimal therapy choice. We investigated the performance fluorescence situ hybridization (FISH) as a diagnostic test for detecting functional fusions.MethodsBetween January 2016 and November 2019, total 4873 NSCLC were routinely screened using either FISH (n = 2858) or targeted RNA next-generation sequencing (NGS) 2015). If sufficient material was available, positive cases analyzed by both methods 39) multiple assays 17). In an independent cohort 520 NSCLC, whole-genome data disruptive structural variations compared ALK ROS1 loci.ResultsFISH analysis revealed rearrangement 48 2858 cases; 30 rearranged double tested NGS, only nine had fusion. NGS yielded 14 2015 all locus rearrangement. Of these 18 verified fusion cases, 16 split signal two complex FISH. By sequencing, prevalence events lower (4 9, 44%) than (27 34, 79%) (9 12, 75%) loci.ConclusionsFISH sensitive but unspecific technique screening, always requiring confirmation orthogonal technique, owing frequently occurring rearrangements not resulting