ALK (anaplastic lymphoma kinase gene), ROS1 (ros proto-oncogene 1) and RET (ret proto-oncogene) fusions are oncogenic drivers in non-small cell lung cancer (NSCLC). Methods like fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) are highly sensitive but subjectively analyzed, labor intensive, expensive and unsuitable for multiple fusion gene screening. This study aimed to establish a high-throughput, sensitive and cost-effective screening method (array-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, array-based MALDI-TOFMS) for ALK, ROS1 and RET fusion detection. This method was established with three fusion gene positive cell lines (H2228, ALK positive; HCC78, ROS1 positive; LC-2/AD, RET positive) and negative samples. Then, 34 clinical samples were selected and detected by Sanger sequencing, next generation sequencing (NGS) and array-based MALDI-TOFMS. The results were compared and analyzed and Sanger sequencing was considered the standard. 7 cases showed ALK fusions, 1 case showed ROS1 fusions, no case showed RET fusions and 4 cases were both ALK and ROS1 fusions. Results showed that array-based MALDI-TOFMS was 100% concordant with Sanger sequencing and NGS 82.3%. In this study, we reported the utility of array-based MALDI-TOFMS in the assessment of ALK, ROS1 and RET fusions in routine lung biopsies of FFPE and fresh tissue specimens. Besides, this method may also be applied to the diagnosis, monitoring and prognosis of illness.
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