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

Acknowledgments

This study was supported in part by grants from the Science and Technology Planning Project of Zhejiang Province (2015C33194) and the National Clinical Key Specialty Construction Program (2013).

Additional information

Funding

This work was supported by the the National Clinical Key Sepcialty Construction Program [2013];the Science and Technology Planning Project of Zhejiang Province [2015C33194];