52P ROS1 aberrations in non-small cell lung cancer patients without rearrangements: Clinical and molecular characteristics

Fusions in the ROS1 proto-oncogene are among the best treatable genetic aberrations in Non-small cell lung cancer (NSCLC). Besides the occurrence of solvent-front mutations (SFM) in acquired resistance to targeted therapy, little is known about ROS1 aberrations other than fusions. We analyzed molecular and clinical characteristics of ROS1 mutations in NSCLC patients without activating ROS1 fusions or SFMs. Next-generation sequencing (NGS) was performed on tissue samples from NSCLC patients within the National Network Genomic Medicine (nNGM). Patients with activating ROS1 fusions detected by fluorescence in-situ hybridization (FISH) were excluded. We analyzed the mutations’ frequencies and characteristics as well as co-occurring mutations. Of 8072 patients analyzed by NGS between 2018 and 2021, 118 (1.5%) patients harbored ROS1 mutations. Most patients were male (76.3%) and had adenocarcinoma histology (57.6%). The median age at diagnosis amounted to 68 years. Nearly all of the patients (96.5%) had a smoking history, amassing 40 pack-years on average. The most frequent ROS1 mutations were transversions (53.6%), without defining a genomic hotspot region. Besides TP53 mutations (61.0%), KRAS (25.4%), EGFR (7.6%), PIK3CA and FGFR1-4 mutations (5.9% each) co-occurred most frequently. In 12 (10.2%) patients, ROS1 mutation was the only detected aberration. Our cohort opposites the clinical characteristics of patients with ROS1 fusion regarding sex, smoking history, age, and histology. Further research is warranted to characterize their biological impact and their potential to act as a drug target.