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Updated: Mar 27, 2026
Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
Published on: October 10, 2025
ROS1 copy number alterations are frequent in non-small cell lung cancer
Sergi Clavé1,2, Javier Gimeno3, Ana M Muñoz-Mármol4
1Laboratori de Citogenètica Molecular, Servei de Patologia, Hospital del Mar, Barcelona, Spain.
Objectives:
We aimed to determine the prevalence and partners of ROS1 rearrangements, to explore the correlation between FISH and IHC assays, and to investigate clinical implications of ROS1 copy number alterations (CNAs).
Methods:
A total of 314 NSCLC patients were screened using ROS1 FISH break-apart probes. Of these, 47 surgical tumors were included in TMAs to analyze ROS1 heterogeneity assessed either by FISH and IHC, and chromosome 6 aneusomy. To characterize ROS1 partners, probes for CD74, EZR, SLC34A2 and SDC3 genes were developed. ROS1 positive FISH cases were screened also by IHC.
Results:
Five patients were ROS1 positive (1.8%). We identified two known fusion partners in three patients: CD74 and SLC34A2. Four out of five ROS1 rearranged patients were female, never smokers and with adenocarcinoma histology. Rearranged cases were also positive by IHC as well. According to ROS1 CNAs, we found a prevalence of 37.8% gains/amplifications and 25.1% deletions.
Conclusions:
This study point out the high prevalence of ROS1 CNAs in a large series of NSCLC. ROS1 gains, amplifications and deletions, most of them due to chromosome 6 polysomy or monosomy, were heterogeneous within a tumor and had no impact on overall survival.
Insights
This study found ROS1 copy number alterations (CNAs) are common in non-small cell lung cancer (NSCLC) but do not impact survival. ROS1 rearrangements were identified in 1.8% of patients, with specific fusion partners noted.
Area of Science:
- Oncology
- Genetics
- Molecular Diagnostics
Background:
- ROS1 rearrangements are key drivers in a subset of non-small cell lung cancer (NSCLC).
- Accurate detection of ROS1 alterations is crucial for targeted therapy selection.
Purpose of the Study:
- Determine the prevalence and fusion partners of ROS1 rearrangements in NSCLC.
- Correlate fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) assay results.
- Investigate the clinical implications of ROS1 copy number alterations (CNAs).
Main Methods:
- Screened 314 NSCLC patients using ROS1 FISH break-apart probes.
- Analyzed 47 surgical tumors for ROS1 heterogeneity and chromosome 6 aneusomy using tissue microarrays (TMAs).
- Developed probes for potential ROS1 fusion partners (CD74, EZR, SLC34A2, SDC3) and screened ROS1-positive FISH cases by IHC.
Main Results:
- Identified ROS1 rearrangements in 1.8% (5/314) of NSCLC patients.
- Confirmed two known fusion partners (CD74, SLC34A2) in three patients.
- Observed high prevalence of ROS1 CNAs: 37.8% gains/amplifications and 25.1% deletions, often linked to chromosome 6 aneuploidy.
Conclusions:
- ROS1 CNAs are prevalent and heterogeneous within NSCLC tumors.
- ROS1 gains, amplifications, and deletions, largely due to chromosome 6 aneuploidy, do not significantly impact overall survival.
- IHC confirmed FISH-detected ROS1 rearrangements, suggesting utility in clinical settings.
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