Analysis of somatic mutations in metastatic ovarian carcinoma and related functional pathways / 第二军医大学学报

ABSTRACT

Objective: To screen the different mutated somatic genes between primary ovarian cancer and metastatic ovarian carcinoma using the whole exon sequencing data of catalogue of somatic mutations in cancer (COSMIC) database, and to analyze their function and signal pathway. Methods: The whole exon sequencing data of all tumors were downloaded from the COSMIC database, and the whole exon sequencing data of all ovarian cancer were extracted. In the R 3.5.3 environment, mutation rate of each mutated gene in the primary and metastatic ovarian carcinoma samples were performed. The χ2 test or Fisher's exact probability method was used to identify the mutated gene groups which had statistically significant difference in mutation rate. The mutated gene groups were further analyzed for gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment. Results: We found a total of 520 somatic mutations with statistically significant differences in mutation rate between primary ovarian cancer and metastatic ovarian carcinoma tissues, such as transmembrane protease serine 13 (TMPRSS13), Golgi brefeldin A resistance factor 1 (GBF1), Fos-like antigen 2 (FOSL2), mastermind-like 3 (MAML3), etc. Enriched GO function included presynapse organization, dendrite development, cell-cell adhesion via plasma membrane adhesion molecules, and actin binding, and so on. KEGG pathway included regulation of actin cytoskeleton, tricarboxylic acid carrier, and the like. Conclusion: It can provide clues for revealing the metastasis regulation mechanism of ovarian cancer by exploring different mutated gene group between primary ovarian cancer and metastatic ovarian carcinoma and its related functional pathways. The significant mutated gene group may be used as biomarkers for the diagnosis and treatment of ovarian metastatic cancer.