Analysis Of Tumor Heterogeneity In High-grade Serous Ovarian Cancer Based On Whole Exome Sequencing

Objective: Use whole exome sequencing(WES)to investigate the tumor-related gene mutations of high-grade serous ovarian cancer,find the differentially expressed mutant genes at different sampling sites,and conduct a preliminary analysis and exploration of the tumor heterogeneity of high-grade serous ovarian cancer.Methods: According to the inclusion and exclusion criteria,3 high-grade serous ovarian cancer patients who were admitted to Lanzhou University First Hospital were selected in this study.Fresh tissue samples were collected from the tumor tissue center and at both ends.The sequencing samples were quickly frozen in a liquid nitrogen tank and then transferred to the-80 refrigerator for storage,and the slice samples were stored in 10% neutral formalin.After the tissue DNA is extracted,the BGI hybridization kit is used to capture the exons,and then sequenced on the BGISEQ-500 platform.After the offline data quality control is qualified,filter,detect and annotate,and then perform single nucleotide polymorphism(SNP)and insertion-deletion(InDel)analysis.Results Compare the NCBI(National Center for Biotechnology Information)gene database,draw the SNP and InDel heat maps of all samples,and finally screen out the differentially expressed mutant genes at different sampling sites according to the gene mutation results,and finally select the samples for immunohistochemical verification.Result:1.Among SNP mutations,missense mutations are the most common.Among them,GC→AT is the most common form of base changes,accounting for 38.9%,39.6%,and 39.6%,respectively.23,21,and 23 SNP sites were screened out of the three groups of samples.After comparing different sampling sites,there were 3differential mutations in sample A and C,and no differential mutation was found in sample B.2.In the results of InDel,insertions or deletions occurred mainly in fragment length of 1-3bp.In the three groups of samples,13,11,and 17 InDel sites were screened separately.After comparing different sampling sites,sample A had 4differential mutations,sample B had 2 differential mutations,and sample C had 8differential mutations.3.In the results of immunohistochemistry,the protein expression in different sampling sites was significantly different(P<0.05).4.A total of 12 mutant genes were screened for SNP and InDel of the 3 sets of samples: FMN2、MAN2B2、ESPNL、SEC16A、MUC6、SIX3、ATP13A5、NOP14、PDLIM2、PPP6C、ITGB3、UNK6.Conclusion:1.Ovarian cancer is a heterogeneous disease.There is heterogeneity not only within the tumor,but also between patients.2.The resulting 12 mutant genes: FMN2,MAN2B2,ESPNL,SEC16 A,MUC6,SIX3,ATP13A5,NOP14,PDLIM2,PPP6 C,ITGB3,UNK6 can be used as potential sites for molecular targeted therapy of ovarian cancer.3.In order to achieve individualized treatment,tumor tissues need to be sampled at multiple points to identify gene mutations at different sites,and then targeted therapy can be carried out.