Simultaneous analysis of ALK, RET, and ROS1 gene fusions by NanoString in Brazilian lung adenocarcinoma patients.

Content Provider	Europe PMC
Author	Novaes, Lázaro Antonio Campanha Sussuchi da Silva, Luciane De Marchi, Pedro Cavagna, Rodrigo de Oliveira de Paula, Flavia Escremim Zanon, Maicon Fernando Evangelista, Adriane Feijó Albino da Silva, Eduardo Caetano Duval da Silva, Vinícius Leal, Letícia Ferro Reis, Rui Manuel
Copyright Year	2021
Abstract	BackgroundGene fusions have been successfully employed as therapeutic targets for lung adenocarcinoma. However, tissue availability for molecular testing of multiples alterations is frequently unfeasible. We aimed to detect the presence of ALK, RET, and ROS1 rearrangements by a RNA-based single assay in Brazilian lung adenocarcinomas and to associate with clinicopathological features and genetic ancestry.MethodsFrom a FFPE series of 444 molecularly characterized lung adenocarcinomas, 253 EGFR/KRAS wild-type cases were eligible for gene rearrangement analysis. Following RNA isolation, ALK, RET, and ROS1 rearrangements were simultaneously analyzed employing the ElementsXT Custom panel (NanoString Technologies). Rearrangements were further associated with clinicopathological features and genetic ancestry of the patients.ResultsThe NanoString platform was performed in subset of 142 cases. Gene fusion results were conclusive for 94.4% (n=134) cases (failure rate =5.6%). ALK rearrangements were observed in 21 out of 134 cases, and associated with younger, never smokers, metastatic disease, and metastases in the central nervous system. RET and ROS1 fusions were detected in two and one out of 134 cases, respectively. Genetic ancestry was not associated with gene fusions. Overall, considering all cases for which a molecular analysis was conclusive (EGFR/KRAS/ALK/RET/ROS1), ALK fusions frequency was observed in 6.5% (21/325), RET in 0.6% (2/325), and ROS1 in 0.3% (1/325).ConclusionsThis study successfully used a RNA-based single assay for the simultaneous analysis of ALK, RET, and ROS1 fusions employing routine biopsies from Brazilian patients lung adenocarcinoma allowing an extensive molecular testing for actionable rearrangements contributing to guide clinical strategies.
ISSN	22186751
Journal	Translational Lung Cancer Research
Volume Number	10
PubMed Central reference number	PMC7867767
Issue Number	1
PubMed reference number	33569313
e-ISSN	22264477
DOI	10.21037/tlcr-20-740
Language	English
Publisher	AME Publishing Company
Publisher Date	2021-01-01
Access Restriction	Open
Rights License	Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0. 2021 Translational Lung Cancer Research. All rights reserved.
Subject Keyword	Non-small cell lung cancer (NSCLC) rearrangements precision medicine multiplexed analysis
Content Type	Text
Resource Type	Article
Subject	Oncology