Retrospective Analysis Of The Relationship Between BRCA,Rad51 Mutations And Recurrence In Patients With Serous Ovarian Cancer And The Treatment Effect Of PARPi

Objective:The paper aims to analyse serous ovarian cancer patients in our hospital.Firstly,gene test wasdone for them,andthe results of detection were examined.Secondly,time to relapse between BRCA mutation-type patients and wild-type patients,and between RAD51 mutation-type patients and nonmutation-type patients were compared after first-line platinum drug treatment.Thirdly,whether the effect ofPARPi（Olaparib）on ovarian cancer patients was related to BRCA and RAD51 genetic mutation was analysed and compared.Also,whether BRCA and RAD51 mutations are important factors which affect the prognosis of ovarian cancer,and based on it,we can provide guidance for patients’ relativeson risk forecast of illness,prevention,and early treatment.Finally,the studycan also provide clinical basis for the therapeutic effectiveness of PARPi on ovarian cancer patients,andthe plans of well-directed treatment for different genotypes of ovarian cancer patients can be made.Methods:In the first step of our study,we collected 37 cases of serous ovarian cancerfrom December 2015 to February 2020,and combinedthe use of target-area capture with second-generation high-throughput sequencing technology to analyse the variation for the 37 cases on exons and adjacent ±20bp intron regions of related genes（including point mutation,deletion and insertion mutation within 20bp）,and calculated the mutation rate of BRCA and RAD51.Then,we utilized SPSS24.0 to examine and compare the age,weight,tumor stage,neoadjuvant chemotherapy,lymph node metastasis,tumor recurrence time,and PFS of the patients whotookPARPi after finishing three-line chemotherapy.After that,based on the clinical data of the patients,wefinished the collection of statistical information about time to relapse for the patients with BRCA and RAD51 mutation and non-mutation after first-line platinum therapy,and evaluated the application effect of PARPi on thepatients who have BRCA and Rad51 mutation and non-mutation.Results:Among all the patients suffering a relapse,there are 12 cases（32.43%）having BRCA genetic mutation,9 cases（24.32%）having BRCA1 genetic mutation,5 cases（13.51%）having BRCA2 genetic mutation,2 cases（5.40%）having both BRCA1 and BRCA2 genetic mutation,and 2 cases（5.40%）having RAD51 mutation,including one case of RAD51 C and one case of RAD51 D mutation.The 2 caseswho suffered both BRCA1 and BRCA2 genetic mutations are not relatives.One case of mutation was onchromosome 18（BRCA1: c.4372 C >T（P.Glu1458Ter））and chromosome 7（BRCA2: c.8958 A > G（p.Ile2986Met））.Another was onchromosome 5（BRCA1: c.387delC（p.Y130TfsX33））and chromosome 11（BRCA2: c.6638C>T（p.S2213F））.There are 3 cases having mutation on chromosome 10: one casebelongs to BRCA2 mutation;the other two cases belong to BRCA1 mutation（c.1012A>T（p.Lys338Ter）and c.1016dupA（p.Val340Glyfs））,while one case of BRCA1 mutation is nonsense mutation,and the restisframeshift mutation.In this study,there were 7 cases of frameshift mutations including 5 cases of BRCA1 mutations which are c.4372C>T（P.Glu1458Ter）,c.387delC（p.Y130TfsX33）,c.3770₃771delAG（p.E1257 G fsX9）,c.237₂38delTA（p.Phe79Leufs）,andc.1016dupA（p.Val340Glyfs）,and 2 cases of BRCA2 mutations which are c.5718₅719delC T（p.Leu1908 Arg fs*2）and c.1568A>G（p.H523R）.Besides,there are 5 cases of missense mutations including 2cases of BRCA1 mutations which are c.4372C>T（p.Q1458X）and c.3596C>T（p.A1199V）,and 3 cases of BRCA2 mutations which arec.8958A>G（p.Ile2986Met）,c.6638C>T（p.S2213F）,and c.6042-6406delTAACT（p.Asn2135lysfs*3）.There are also 2 cases of nonsense mutations belonging to BRCA1 mutations which arec.604C>T（p.GIn202Ter）,c.1012A>T（p.Lys338Ter）.In our research,2 cases of RAD51 mutations are found,which includes one case of RAD51 C mutation（c.14G>A（p.Trp5*）,missense mutation）,and one case of RAD51 D mutation（c.3564delC（p.Phe1189 Le ufs*10）,frameshift mutation）.The study shows that the existence of BRCAgenetic mutations and RAD51 genetic mutations makes no statistical sense（P>0.05）of weight,onset age,lymph node metastasis,and tumor stage to all the 37 cases;there is no difference in CA125 value between the patientswith RAD51 mutation and those with non-mutation（P>0.05）;there is no difference in diseaserecurrence interval（P > 0.05）whether neoadjuvant chemotherapy was applied or not.In addition,the CA125 value of the patients with BRCA mutation was lower than that of the patients without BRCA mutation（P < 0.05）;disease recurrence interval of the patients with BRCA and RAD51 mutation was longer than that of the patients with no BRCA and RAD51mutation（P < 0.05）;the curative effectofPARPi on the patients with BRCA mutation was better compared with the patients with noBRCA mutation,and Progression-Free Survival（PFS）of the patients with BRCA mutation is also longer（P < 0.05）;there is better curative effect of PARPi on the patients with RAD51 mutation compared with the patients with HRD（-）,and Progression-Free Survival（PFS）of the patients with HRD（+）（RAD51positive）is also longer（P < 0.05）.Conclusion:1.Disease recurrence interval of ovarian cancer patients with BRCA and RAD51 genetic mutations is prolonged compared to those with no mutations.Whether there are BRCA gene mutation and RAD51 mutation or not is factors which affect the prognosis of ovarian cancer significantly.2.The patients with BRCA and RAD51 mutations more likely benefit from PARPi than those with no mutations,andPFSofthe patients with BRCA and RAD51 mutations was prolongednoticeably.3.BRCA and RAD51 gene test for early-stage ovarian cancer patients can be helpful todevelop well-directed treatment strategies and evaluate the curative effect.Also,afteradvanced ovarian cancerpatients are treated,asking them to take targetingdrugs like PARPi can achieve the prolongation of PFS.