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

Abstract

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.

Next-generation sequencing impact on cancer care: applications, challenges, and future directions

“…Studies on genome-wide analyses, like The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) performed with NGS technology, provided comprehensive mutational data ( Nakagawa and Fujita, 2018 ). Such advanced technology does not limit itself to a single tumor site and may be applied to Non-Small Lung Cell Cancer (NSLCC) ( de Oliveira Cavagna et al, 2023 ; Kang et al, 2024 ), Colon Cancer ( Zhu L. et al, 2023 ; Bachet et al, 2023 ; Quintanilha et al, 2023 ), and Melanoma ( King et al, 2023 ; Perez-Perez et al, 2023 ; Dedeilia et al, 2024 ) care.…”