The Clinical Application Of Whole Exome Sequencing Technology In High Grade Serous Ovarian Cancer HRR Pathway And The Drug Resistance Mutation Detection

Objective: Use whole-exome sequencing(WES)technology research the mutations of HRR pathway and resistance genes in high-grade serous ovarian cancer patients,and guide the clinical treatment.Methods: Screening of 15 high-grade serous ovarian patients in this study,tissue samples are from the Fourth Hospital of Hebei Medical University.DNA was first extracted from the fresh surgical tissues of these 15 patients.Then to library building,library quality inspection and sequencing.Finally,biological analysis of sequencing data,related gene screening of HRR pathway.Results:1.Genome-wide bases in conversion/transversion ratio is 2.34,compared to the reference genome and in the right direction reads ratio achieves 98%,cover depth of not less than 10 x bases in the target area in 98% and 99%,the proportion of SNP data set in line with the accuracy.2.This study obtained the 15 patients with HGSOC fresh tissue samples of WES sequencing data,somatic mutations SNV mainly gathered in the C>A/G>T in the sample.3.In these 15 HGSOC patients,each have 10 patients occur TP53,BRCA1/2 mutations,mutation rate is 66.7%,they are associated with DNA repair,TP53 is high frequency mutation among them.4.PI3K-AKT,WNT,VEGF,MAPK,TP53 signaling pathway mutations are found in the sample,involved in the activation of proto-oncogenes and the inactivation tumor of tumor suppressor genes.5.14 HGSOC patients occur HRR pathway mutation,some patients occur BER,MMR,NER pathway mutation.6.2 HGSOC patients exist the drug resistance loci of BRCA2 mutation,likely to exist drug resistance in platinum based chemotherapy.Conclusions:1.TP53 is high frequency mutation,BRCA1/2 are the main mutations in HRR pathway,the mutation frequency of HRR pathway related genes is low,such as RAD50,RAD51,RAD54 B,XRCC2,etc.2.Based on the genetic mutations associated with HRR pathway,targeted drugs can bring benefit to high-grade serous ovarian patients,such as olaparib,applicable to the BRCA mutation.3.Drug resistance testing of genetic mutations in high-grade serous ovarian patients is expected to accurate guide subsequent clinical treatment.4.Signaling pathway mutations,such as PI3K-AKT,WNT,VEGF,MAPK,TP53,involve in cell growth and all aspects of the life activities.