Development of a high-throughput and sensitive assay of fusion genes in lung cancer by array-based MALDI-TOFMS.

ALK (anaplastic lymphoma kinase gene), () and () fusions are oncogenic drivers in non-small cell lung cancer (NSCLC). Methods like fluorescence 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 , and fusion detection. This method was established with three fusion gene positive cell lines (H2228, positive; HCC78, positive; LC-2/AD, 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 fusions, 1 case showed fusions, no case showed fusions and 4 cases were both and 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 , and 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.