Detection of NTRK fusions by RNA-based nCounter is a feasible diagnostic methodology in a real-world scenario for non-small cell lung cancer assessment

• Published in: Scientific reports Vol. 13; no. 1; p. 21168
• Main Authors: de Oliveira Cavagna, Rodrigo, de Andrade, Edilene Santos, Tadin Reis, Monise, de Paula, Flávia Escremim, Noriz Berardinelli, Gustavo, Bonatelli, Murilo, Ramos Teixeira, Gustavo, Garbe Zaniolo, Beatriz, Mourão Dias, Josiane, da Silva, Flávio Augusto Ferreira, Baston Silva, Carlos Eduardo, Xavier Reis, Marina, Lopes Maia, Erika, de Alencar, Thainara Santos, Jacinto, Alexandre Arthur, da Nóbrega Oliveira, Rachid Eduardo Noleto, Molina-Vila, Miguel A., Ferro Leal, Letícia, Reis, Rui Manuel
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 631/208/721; 631/67; 631/67/1612; 631/67/1612/1350; 631/67/1857; 631/67/68; 692/53/2421; Adenocarcinoma; Adenocarcinoma of Lung; ALK protein; Biopsy; Carcinoma, Non-Small-Cell Lung - diagnosis; Carcinoma, Non-Small-Cell Lung - genetics; Gene fusion; Humanities and Social Sciences; Humans; Immunohistochemistry; Lung cancer; Lung Neoplasms - diagnosis; Lung Neoplasms - genetics; multidisciplinary; Next-generation sequencing; Non-small cell lung carcinoma; NTRK3 gene; Oncogene Proteins, Fusion - genetics; Receptor, trkA - genetics; Ribonucleic acid; RNA; Science; Science (multidisciplinary); Small cell lung carcinoma; Therapeutic targets
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-48613-4

NTRK1, 2, and 3 fusions are important therapeutic targets for NSCLC patients, but their prevalence in South American admixed populations needs to be better explored. NTRK fusion detection in small biopsies is a challenge, and distinct methodologies are used, such as RNA-based next-generation sequencing (NGS), immunohistochemistry, and RNA-based nCounter. This study aimed to evaluate the frequency and concordance of positive samples for NTRK fusions using a custom nCounter assay in a real-world scenario of a single institution in Brazil. Out of 147 NSCLC patients, 12 (8.2%) cases depicted pan-NTRK positivity by IHC. Due to the absence of biological material, RNA-based NGS and/or nCounter could be performed in six of the 12 IHC-positive cases (50%). We found one case exhibiting an NTRK1 fusion and another an NTRK3 gene fusion by both RNA-based NGS and nCounter techniques. Both NTRK fusions were detected in patients diagnosed with lung adenocarcinoma, with no history of tobacco consumption. Moreover, no concomitant EGFR , KRAS, and ALK gene alterations were detected in NTRK -positive patients. The concordance rate between IHC and RNA-based NGS was 33.4%, and between immunohistochemistry and nCounter was 40%. Our findings indicate that NTRK fusions in Brazilian NSCLC patients are relatively rare (1.3%), and RNA-based nCounter methodology is a suitable approach for NRTK fusion identification in small biopsies.