Novel mutations of SYK gene in solid tumors.

Abstract

e13519 Background: Spleen tyrosine kinase ( SYK) is a non-receptor tyrosine kinase (NRTK) in cytoplasmic and plays a crucial role in multiple signaling pathways. The deletion of SYK gene expression will lead to the formation and metastasis of multiple solid tumors. Previous studies focus on the methylation of the SYK gene promoter and the protein isomers, including SYK (L) and SYK (S) which are differed by 23 amino acids in functional domains. Nevertheless, the knowledge of mutations in SYK remains poorly understood. Herein, next generation sequencing were performed to explore SYK mutations for further clinical research. Methods: We retrospectively analyzed the somatic mutations from a comprehensive genomic profiling in tumor tissue or blood ctDNA of 4,093 patients with pan-cancer, of which 2,213 patients using 528 genes panel and 1,880 patients using 539 genes panel, both of the panels contained all exon regions of SYK gene. SYK mutations analyzed by TCGA database was used as validation to our results. Results: In 4093 patients with pan-carcinoma, 36 patients were found mutations in SYK gene and the mutation frequency was 0.880%, of which 4 intron mutations and 32 cases of exon mutations were found in patients, respectively. A number of 9 mutations might affect protein function, which were stop-gained mutations and frameshift mutations and their proportion was 0.220%. The mutation frequency of SYK was consistent with TCGA. Among 9 mutations, 3 mutations were also found in TCGA, which were R574*, M34fs, E376*, respectively. And the rest 6 mutations were newly found, which were V395fs, N615fs, Y74*, G185*, Y74fs, Q145*, respectively. Colorectal cancer was the most common cancer type harboring SYK mutations, and TP53 was the most frequently co-mutated gene of SYK which was counted 5 both in our detected results and in TCGA database. Conclusions: Firstly report of 6 novel stop-gained and frame-shift mutations in SYK gene expanded the understanding of SYK in solid tumors. As a retrospective study in pan-cancer with a relatively small population and the mechanism is unclear, the conclusions of this study needed to be verified with a larger sample.