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RET Fluorescence In Situ Hybridization Analysis Is a Sensitive but Highly Unspecific Screening Method for RET Fusions in Lung Cancer
- Source :
- Radonic, T, Geurts-Giele, W R R, Samsom, K G, Roemen, G M J M, von der Thüsen, J H, Thunnissen, E, Meijssen, I C, Sleddens, H F B M, Dinjens, W N M, Boelens, M C, Weijers, K, Speel, E J M, Finn, S P, O'Brien, C, van Wezel, T, Cohen, D, Monkhorst, K, Roepman, P & Dubbink, H J 2021, ' RET Fluorescence In Situ Hybridization Analysis Is a Sensitive but Highly Unspecific Screening Method for RET Fusions in Lung Cancer ', Journal of Thoracic Oncology, vol. 16, no. 5, pp. 798-806 . https://doi.org/10.1016/j.jtho.2021.01.1619, Journal of Thoracic Oncology, 16(5), 798-806. Elsevier Science, Journal of Thoracic Oncology, 16(5), 798-806. International Association for the Study of Lung Cancer
- Publication Year :
- 2021
-
Abstract
- Introduction: RET gene fusions are established oncogenic drivers in 1% of NSCLC. Accurate detection of advanced patients with RET fusions is essential to ensure optimal therapy choice. We investigated the performance of fluorescence in situ hybridization (FISH) as a diagnostic test for detecting functional RET fusions.Methods: Between January 2016 and November 2019, a total of 4873 patients with NSCLC were routinely screened for RET fusions using either FISH (n = 2858) or targeted RNA next-generation sequencing (NGS) (n = 2015). If sufficient material was available, positive cases were analyzed by both methods (n = 39) and multiple FISH assays (n = 17). In an independent cohort of 520 patients with NSCLC, whole-genome sequencing data were investigated for disruptive structural variations and functional fusions in the RET and compared with ALK and ROS1 loci.Results: FISH analysis revealed RET rearrangement in 48 of 2858 cases; of 30 rearranged cases double tested with NGS, only nine had a functional RET fusion. RNA NGS yielded RET fusions in 14 of 2015 cases; all nine cases double tested by FISH had RET locus rearrangement. Of these 18 verified RET fusion cases, 16 had a split signal and two a complex rearrangement by FISH. By whole-genome sequencing, the prevalence of functional fusions compared with all disruptive events was lower in the RET (4 of 9, 44%) than the ALK (27 of 34, 79%) and ROS1 (9 of 12, 75%) loci.Conclusions: FISH is a sensitive but unspecific technique for RET screening, always requiring a confirmation using an orthogonal technique, owing to frequently occurring RET rearrangements not resulting in functional fusions in NSCLC. (C) 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc.
- Subjects :
- 0301 basic medicine
Pulmonary and Respiratory Medicine
congenital, hereditary, and neonatal diseases and abnormalities
endocrine system
endocrine system diseases
Sequencing data
MULTICENTER
Locus (genetics)
ROS1 REARRANGEMENT
03 medical and health sciences
0302 clinical medicine
FISH
medicine
ROS1
Screening method
Lung cancer
neoplasms
medicine.diagnostic_test
business.industry
RET Rearrangement
medicine.disease
Molecular biology
030104 developmental biology
Oncology
ALK
030220 oncology & carcinogenesis
Fish
RNA NGS
Non-small cell carcinoma
business
RET
Fluorescence in situ hybridization
Subjects
Details
- Language :
- English
- ISSN :
- 15560864
- Volume :
- 16
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Journal of Thoracic Oncology
- Accession number :
- edsair.doi.dedup.....0b1e428c89911a1ba266b62b3867f640