Association Of Mutations In BRCA2 Domains And Acquired Platinum Resistance After Neoadjuvant Chemotherapy In Patients With Advanced Ovarian Cancer

PURPOSE:The object of this study was to detect the mutation of BRCA2 domains in epithelial ovarian cancer(EOC) with primary debulking surgery and neoadjuvant chemotherapy interval debulking surgery,to further investigation the mechanism of acquired-platinum-resistance after neoadjuvant chemotherapy in EOC, and to provide a new guidance for the treatment of strategy.METHODS:1.Ovarian tissue DNA of 64 patients with serous ovarian were extracted.2.Detected the sequences of BRCA2 domains by nested-polymerase-chain-reaction (Nested-PCR) in 64 advanced EOC(primary debulking surgery, N=30; neoadjuvant chemotherapy interval debulking surgery, N=34) with FIGO Ⅲ-Ⅳ.3.Collected the information about patients’and tumor features.The correlation between BRCA2 domains mutations and platinum resistance and platinum-resistance after neoadjuvant chemotherapy in EOC was analyzed. And the relationship of clinical pathological information and BRCA2 domains mutations between prognosis in EOC was analyzed.RESULTS:1.28 of 64 BRCA2 domains mutations were detected(silent mutation:N=4; missense mutation:N=19; nonsense mutation:N=5).2. Distinct mutations were detected in PDS(silent mutation:N=1; missense mutation:N=10; nonsense mutation:N=5,53.33%). And the percentage of NACT-IDS was 35.29%(silent mutation:N=3; missense mutation:N=9; nonsense mutation:N=0).3. BRCA2 domains mutation was associated with response of platinum (P=0.02) and BRCA2 domains nonsense mutation also contacted with acquired-platinum-resistance after neoadjuvant chemotherapy in EOC (P=0.0367). BRCA2 domains mutation was correlated with prognosis of patients with EOC. Univariate and multivariate analysis revealed that BRCA2 nonsense mutation was significantly correlated with overall survival in patients with EOC(P=0.023).CONCLUSION:Detect the mutation of BRCA2 domains in EOC provided an important reference for making a better treatment decision and evaluating the prognosis. A better understanding about the relationship between BRCA2 and platinum-resistance in EOC could improve the treatment prognosis.