A novel co-existing ZCCHC8-ROS1 and de-novo MET amplification dual driver in advanced lung adenocarcinoma with a good response to crizotinib

Abstract

In non-small cell lung cancer (NSCLC), driver gene alterations, such as EGFR, ALK, MET, and ROS1, are usually mutually exclusive. Few clinical cases with co-existing ROS1 fusion and de-novo MET amplification have been reported. In addition, the efficacy of crizotinib in Chinese patients with driver co-existing alterations is uncertain. A 65-year-old female was diagnosed with lung adenocarcinoma metastatic to the brain. She had sufficient tumor tissue for detection of the target gene; however, common driver gene mutations, such as EGFR-wild and ALK-negative, were not initially detected. The patient was ultimately shown to have both ZCCHC8-ROS1 and de-novo MET gene amplification through next-generation sequencing with sensitivity to the targeted therapy of crizotinib. Unfortunately, the progression-free survival was only 6 months in length. We report here the first patient with co-existing ROS1 fusion and de-novo MET amplification to receive crizotinib in China. Treatment of our patient was effective with targeted therapy based on a precise diagnosis. Advanced or metastatic NSCLC patients with co-existing ROS1 fusion and de-novo MET amplification are sensitive to crizotinib. These uncommon driver gene mutations may be missed using the current first-generation detection assay. We must be aware of the incidence of concomitant ROS1 fusion and de-novo MET amplification because NSCLC patients could benefit from targeted therapy.

Keywords

• NSCLC
• ZCCHC8-ROS1 fusion
• MET amplification
• next-generation sequencing