CEP72-ROS1: A novel ROS1 oncogenic fusion variant in lung adenocarcinoma identified by next-generation sequencing
You-Cai Zhu1, Yue-Fen Zhou2, Wen-Xian Wang3
1Chest Disease Diagnosis and Treatment Center, Zhejiang Rongjun Hospital, Jiaxing, China.
Abstract:
ROS1 rearrangement is a validated therapeutic driver gene in non-small cell lung cancer (NSCLC) and represents a small subset (1-2%) of NSCLC. A total of 17 different fusion partner genes of ROS1 in NSCLC have been reported. The multi-targeted MET/ALK/ROS1 tyrosine kinase inhibitor (TKI) crizotinib has demonstrated remarkable efficacy in ROS1-rearranged NSCLC. Consequently, ROS1 detection assays include fluorescence in situ hybridization, immunohistochemistry, and real-time PCR. Next-generation sequencing (NGS) assay covers a range of fusion genes and approaches to discover novel receptor-kinase rearrangements in lung cancer. A 63-year-old male smoker with stage IV NSCLC (TxNxM1) was detected with a novel ROS1 fusion. Histological examination of the tumor showed lung adenocarcinoma. NGS analysis of the hydrothorax cellblocks revealed a novel CEP72-ROS1 rearrangement. This novel CEP72-ROS1 fusion variant is generated by the fusion of exons 1-11 of CEP72 on chromosome 5p15 to exons 23-43 of ROS1 on chromosome 6q22. The predicted CEP72-ROS1 protein product contains 1202 amino acids comprising the N-terminal amino acids 594-647 of CEP72 and C-terminal amino acid 1-1148 of ROS1. CEP72-ROS1 is a novel ROS1 fusion variant in NSCLC discovered by NGS and could be included in ROS1 detection assay, such as reverse transcription PCR. Pleural effusion samples show good diagnostic performance in clinical practice.
Insights
A novel CEP72-ROS1 fusion was discovered in non-small cell lung cancer (NSCLC) using next-generation sequencing. This finding expands the known ROS1 rearrangements and may improve diagnostic assays for NSCLC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- ROS1 rearrangements are key drivers in a small subset of non-small cell lung cancer (NSCLC).
- Crizotinib is an effective tyrosine kinase inhibitor for ROS1-rearranged NSCLC.
- Current detection methods include FISH, IHC, and real-time PCR, with next-generation sequencing (NGS) offering broader gene coverage.
Observation:
- A 63-year-old male smoker with stage IV NSCLC presented with a novel ROS1 fusion.
- Histological examination confirmed lung adenocarcinoma.
- NGS analysis of hydrothorax cellblocks identified a previously unreported CEP72-ROS1 rearrangement.
Findings:
- The novel CEP72-ROS1 fusion involves exons 1-11 of CEP72 and exons 23-43 of ROS1.
- The predicted protein product comprises specific N-terminal and C-terminal amino acid sequences from CEP72 and ROS1, respectively.
- This fusion variant was identified using NGS in pleural effusion samples.
Implications:
- The discovery of the CEP72-ROS1 fusion expands the landscape of known ROS1 alterations in NSCLC.
- This novel variant could be incorporated into existing ROS1 detection assays, such as reverse transcription PCR.
- Utilizing pleural effusion samples demonstrates diagnostic utility in clinical practice for identifying such fusions.
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