Comparison of fusions detection by next generation sequencing between malignant pleural effusion and tumor tissue in lung cancer.

Abstract

e21059 Background: Anaplastic lymphoma kinase ( ALK), c-ros oncogene 1 receptor tyrosine kinase ( ROS1), ret proto-oncogene ( RET) and neurotrophic receptor kinase ( NTRK) are important driver genes in lung cancer. Each of these four genes fusions as therapeutic targets have been recommended by the national comprehensive cancer network (NCCN) guidelines for non-small cell lung cancer (NSCLC). Malignant pleural effusion (MPE) is observed in multy types of malignancies, especially in lung cancer. Studies have indicated that next generation sequencing (NGS) detection of somatic mutations by MPE is reliable. Nevertheless, the distribution and comparison of fusions in lung cancer between malignant pleural effusion and tumor tissue specimen have not been well characterized yet. Methods: In this study, 9-gene, 69-gene and 539-gene panel NGS profiling were performed by MPE and tumor tissue in 640 and 10013 patients with lung cancer respectively. The variation analysis between patients with or without gene fusion in different sample groups were calculated by fisher exact test via SPSS v26.0. Results: In lung cancer patients using MPE detection, 59 of 640 (9.22%) were found harboring at least one of the four gene fusions, and the ratio of ALK, ROS1, RET and NTRK fusion was 6.25% (40/640), 1.41% (9/640), 0.63% (4/640) and 0.47% (3/640) respectively. Meanwhile, we found gene fusions in 6.25% (626/10013) lung cancer patients using tumor tissue detection, including 3.66% (366/10013) ALK fusion, 1.07% (107/10013) ROS1 fusion, 1.09% (108/10013) RET fusion and 0.22% (626/10013) NTRK fusion. Significant differences of gene fusion frequency between different sample groups were found via fisher exact test ( p = 0.005), especially ALK fusion ( p = 0.001). Conclusions: The frequency of fusion in MPE was significantly higher than in tumor tissue, especially ALK fusion. However, as a retrospective study, the conclusions and the specific mechanisms are needed to be verified.