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P2.03 - Biology (ID 162)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
P2.03-27 - Discovery of WNK1-ROS1 Fusion in a Lung Adenocarcinoma Patient and the Precise Guidance for Targeted Therapies (ID 2122)
10:15 - 18:15 | Author(s): Tianfeng Liu
Lung cancer can be driven by activation of tyrosine kinases including EGFR mutations, ALK, ROS1, RET, or NTRK fusions. New partners of gene fusions remain to be identified and their response to targeted therapy need be carefully evaluated in the clinical practice.Method
A targeted next-generation sequencing (NGS) panel was used to analyze DNA extracted from tumor tissue and plasma samples from a lung adenocarcinoma patient. The fusion detected by NGS panel was confirmed by Sanger sequencing.Result
Using a targeted NGS lung cancer panel, we identified a novel ROS1 fusion from a 39-year old Chinese female with lung adenocarcinoma. No EGFR, MET, KRAS, ALK, ROS1 or other driver mutations of lung cancer were detected in the patient. Intron 25 of WNK1 was translocated to intron 33 of ROS1 (Figure blow), which resulted in an in-frame fusion transcript of WNK1-ROS1 at the breakpoints of exon 25 and exon 34, respectively. Sanger sequencing confirmed the fusion and the breakpoints. This novel WNK1-ROS1 fusion encoded a chimera protein of which the transmembrane and kinase domains of ROS1 remained intact. The patient received treatment with crizotinib targeting to ROS1, and partial response was achieved 3 months later. Resistance to crizotinib occurred at 5 months after the treatment. Analysis of the ctDNA from the patient’s plasma sample identified ROS1 G2032R mutation, a well-known mechanism of ROS1 resistance to crizotinib. The patient was subsequently treated with TPX-0005, which is effective to ROS1 G2032R mutant. Decreased CEA level was observed 2 months after TPX-0005 treatment, suggesting the patient was responsive to the targeted therapy.
We identified a lung adenocarcinoma patient with a novel WNK1-ROS1 fusion who was sensitive to crizotinib and developed crizotinib resistant ROS1 G2032R mutation at progression but appeared to be responsive to the new generation of TPX-0005 therapy. These results suggest that WNK1-ROS1 fusion is a new molecular mechanism leading to lung adenocarcinoma and targetable to ROS1 tyrosine kinase inhibitors.
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