2024 World Conference on Lung Cancer (WCLC) - ePosters-EP.06F.06 Concurrent DNA and RNA NGS Testing to Characterize Rare Fusions in Advanced NSCLC Patients

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The study explores the use of concurrent DNA and RNA next-generation sequencing (NGS) to identify rare gene fusions in patients with advanced non-small cell lung cancer (NSCLC) from the Tempus multi-modal database. The analysis included 5,570 advanced NSCLC patients who underwent both DNA-seq and RNA-seq to assay known cancer-related mutations and potential emerging structural variants (eSVs).<br /><br />The concurrent approach, utilizing Tempus xT (DNA-seq) and xR (RNA-seq) assays, aimed to enhance the detection of fusions that may serve as actionable targets for therapy. The assays screened for established variants such as ALK, RET, ROS1, and NTRK fusions, and also identified rare gene fusions in BRAF, NRG1, and EGFR, increasing the detection rate of these rare variants when compared to DNA-seq alone. Notably, 50% of detected BRAF fusions co-occurred with common EGFR activating mutations in patients who had received tyrosine kinase inhibitors (TKIs). <br /><br />The study highlighted a significant increase in the detection of rare fusion variants using dual-sequencing methods, potentially impacting the clinical management of NSCLC by identifying novel drug targets. The detected BRAF fusions, possibly representing a resistance mechanism, open up avenues for new therapeutic strategies upon failure of initial treatments.<br /><br />The analysis concentrated on the demographic and clinical characteristics of patients with and without eSVs, revealing differences in smoking status and co-occurring mutations. Ultimately, the combination of DNA and RNA sequencing techniques demonstrated a refined ability to capture actionable mutations, providing a richer dataset for individualized patient treatment strategies and advancing the understanding of molecular drivers in NSCLC.

Asset Subtitle

Josephine Feliciano

Meta Tag

Speaker Josephine Feliciano

Topic Pathology and Biomarkers

Keywords

concurrent sequencing

DNA RNA NGS

rare gene fusions

non-small cell lung cancer

Tempus database

actionable targets

BRAF fusions

tyrosine kinase inhibitors

dual-sequencing methods

individualized treatment