Whole Exome Sequencing Reveals Potential Single Nucleotide Polymorphisms and Copy Number Variations in 26 Sporadic Patients with Immature Teratoma

全外显子组测序揭示了26例散发性未成熟畸胎瘤患者中潜在的单核苷酸多态性和拷贝数变异

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Abstract

BACKGROUND: Immature teratoma is a malignant tumor and accounts for 1%-3% of ovary teratoma. The objective of this study was to find the potential single nucleotide polymorphisms (SNPs), copy number variations (CNVs) and drug targets in the immature teratoma. MATERIAL AND METHODS: Genomic DNA was extracted from peripheral blood of 26 sporadic immature teratoma patients for whole exome sequencing (WES) analysis to detect germline variants. SNPs and CNVs were identified, followed by the analysis of physical/chemical properties and conserved domain of mutated genes. Functional enrichment and protein-protein interaction (PPI) analysis of mutated genes was performed, followed by pharmacogenomic analysis. Finally, SNPs, CNVs and mRNA expression of mutated genes were investigated in ovarian cancer by using the online databases. RESULTS: A total of 24 common mutated genes were identified in 26 patients. Among which, 5 common mutated genes with common mutation sites were identified, including 2 frameshift mutant genes (MYPOP and FRG2C) and 3 nonsynonymous mutant genes (CNTNAP3, GPRIN2 and MUC3A). After mutation, molecular weight of MYPOP, FRG2C, CNTNAP3, GPRIN2 and MUC3A changed slightly. In the PPI network, MUC12 (with the highest degree) interacted with GALNT12, MUC3A and FCGBP. Based on the pharmacogenomic analysis, MUC2 was predicted to be a potential drug target of CHEMBL35482, FLUOROURACIL and DECITABINE. According to the functional analysis, MUC3A, MUC2 and MUC12 were involved in biological processes of activation of the innate immune response. The mutation frequency of FCGBP and CNTNAP3 was rare and had a higher amplification frequency in ovarian cancer. In addition, 2 common CNVs (deletion state) were screened out, which involving 6 genes, such as RP11. CONCLUSION: This study identified some potential SNPs and CNVs, which may contribute to clarifying the pathogenesis of immature teratoma and provide potential biomarkers and drug targets for this disease.

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