Rationale for Correct Answer

The correct answer is: RNA-based NGS

RNA-based NGS is the most straightforward method for detecting novel tyrosine kinase fusions that might be targetable in patients with advanced NSCLC. DNA-based NGS can also identify novel fusions but is hampered by the need to sequence through sometimes lengthy and repetitive introns, leading to underdetection of both known and novel fusions (false negatives).1 FISH can detect novel fusions but is associated with a high level of false positives and false negatives.1,2 Sanger sequencing is not a National Comprehensive Cancer Network (NCCN)-recommended method for detecting known or novel gene fusions in NSCLC.2

1. Benayed R et al. Clin Cancer Res. 2019;25:4712-4722.
2. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer. Version 3.2023. Updated April 13, 2023. Available at: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1450