Pan-tumor survey of ROS1 fusions detected by next-generation RNA and whole transcriptome sequencing
Misako Nagasaka1,2,3, Shannon S Zhang4, Yasmine Baca5
1Department of Medicine, Division of Hematology and Oncology, University of California Irvine School of Medicine, 200 South Manchester Ave, Orange, CA, 92868, USA. nagasakm@hs.uci.edu.
Background:
Two ROS1 tyrosine kinase inhibitors have been approved for ROS1 fusion positive (ROS1+) non-small cell lung cancer (NSCLC) tumors. We performed a pan-tumor analysis of the incidence of ROS1 fusions to assess if more ROS1+ patients who could benefit from ROS1 TKIs could be identified.
Methods:
A retrospective analysis of ROS1 positive solid malignancies identified by targeted RNA sequencing and whole transcriptome sequencing of clinical tumor samples performed at Caris Life Science (Phoenix, AZ).
Results:
A total of 259 ROS1+ solid malignancies were identified from approximately 175,350 tumors that underwent next-generation sequencing (12% from targeted RNA sequencing [Archer]; 88% from whole transcriptome sequencing). ROS1+ NSCLC constituted 78.8% of the ROS1+ solid malignancies, follow by glioblastoma (GBM) (6.9%), and breast cancer (2.7%). The frequency of ROS1 fusion was approximately 0.47% among NSCLC, 0.29% for GBM, 0.04% of breast cancer. The mean tumor mutation burden for all ROS1+ tumors was 4.8 mutations/megabase. The distribution of PD-L1 (22C3) expression among all ROS1+ malignancies were 0% (18.6%), 1%-49% (29.4%), and ≥ 50% (60.3%) [for NSCLC: 0% (17.8%); 1-49% (27.7%); ≥ 50% (53.9%). The most common genetic co-alterations of ROS1+ NSCLC were TP53 (29.1%), SETD2 (7.3%), ARIAD1A (6.3%), and U2AF1 (5.6%).
Conclusions:
ROS1+ NSCLC tumors constituted the majority of ROS1+ solid malignancies with four major fusion partners. Given that > 20% of ROS1+ solid tumors may benefit from ROS1 TKIs treatment, comprehensive genomic profiling should be performed on all solid tumors.
Insights
This study identified ROS1 fusions in various solid tumors, with non-small cell lung cancer being the most common. Comprehensive genomic profiling may help identify more patients eligible for ROS1 tyrosine kinase inhibitor treatment.
Area of Science:
- Oncology
- Genomics
- Precision Medicine
Background:
- Two ROS1 tyrosine kinase inhibitors (TKIs) are approved for ROS1 fusion-positive (ROS1+) non-small cell lung cancer (NSCLC).
- A pan-tumor analysis was conducted to identify more ROS1+ patients who could benefit from ROS1 TKIs.
Purpose of the Study:
- To assess the incidence of ROS1 fusions across various solid tumor types.
- To determine the potential for broader application of ROS1 TKIs beyond NSCLC.
Main Methods:
- Retrospective analysis of ROS1+ solid malignancies.
- Utilized targeted RNA sequencing and whole transcriptome sequencing of clinical tumor samples.
Main Results:
- Identified 259 ROS1+ solid malignancies from ~175,350 tumors.
- ROS1+ NSCLC comprised 78.8% of cases, followed by glioblastoma (6.9%) and breast cancer (2.7%).
- ROS1 fusion frequencies were 0.47% in NSCLC, 0.29% in GBM, and 0.04% in breast cancer.
Conclusions:
- ROS1+ NSCLC is the predominant malignancy with ROS1 fusions.
- Over 20% of ROS1+ solid tumors may benefit from ROS1 TKI treatment.
- Comprehensive genomic profiling is recommended for all solid tumors to identify potential candidates for ROS1 TKI therapy.
