Homologous Recombination Inquiry Through Ovarian Malignancy Investigations: The Japanese Gynecologic Oncology Group study JGOG3025

The Cancer Genome Atlas has clarified that about 50% of high-grade serous ovarian cancer shows homologous recombination deficiency (HRD). However, the frequency of HRD in Japanese patients with ovarian cancer remains unclear. The aim of JGOG3025 study ([NCT03159572][1]) is to identify the frequency of HRD in Japanese patients with ovarian cancer. The JGOG3025 study is a multicenter collaborative prospective observational study involving 65 study sites throughout Japan. We recruited 996 patients who were clinically diagnosed with ovarian cancer before surgery from March 2017 to March 2019, and 701 patients were eligible for JGOG3025 criteria. We used frozen tumor tissues to extract DNA and performed targeted sequencing for 51 genes most of which are HR-associated genes in 701 ovarian cancers (298 high-grade serous, 189 clear cell, 135 endometrioid, 12 mucinous, 3 low-grade serous, and 64 others). HRD was defined as positive when at least one HR-associated gene was mutated. The frequencies of HRD and tumor BRCA1/2 mutation were 45.2% (317/701) and 18.5% (130/701) in the full analysis set (FAS), respectively. Next, we performed multivariate Cox proportional hazards regression analysis for progression-free survival (PFS) and overall survival (OS). Advanced-stage ovarian cancer patients with HRD had an adjusted hazard ratio of 0.72 (95%CI, 0.55-0.93) and 0.58 (95%CI, 0.39-0.87) for PFS and OS compared to those without HRD (p = 0.013 and 0.009). Our study demonstrated that mutations in HR-associated genes might be associated with their prognosis. Further study will be needed to investigate prognostic impact of each HR-associated gene in ovarian cancer. ### Competing Interest Statement Although KY received only lecture fees from Astrazeneca, he has no other conflicts of interest to declare. ### Funding Statement AstraZeneca Externally Sponsored Research. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Ethics Committee of the Japanese Gynecologic Oncology Group (JGOG) gave ethical approval for this work (JGOG3025). The Institute Review Board of Niigata University also gave ethical approval for this work (2006-0006). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors. * aHR : adjusted hazard ratio CI : Confidence Interval FAS : Full analysis set FIGO : International Federation of Gynecology and Obstetrics GI : Genomic Instability HR : homologous recombination HRD : homologous recombination deficiency JGOG : Japanese Gynecologic Oncology Group MSI : Microsatellite instability NAC : Neoadjuvant chemotherapy OS : Overall survival PARP : poly (ADP-ribose) polymerase PFS : Progression free survival PS : Performance status SNV : Single nucleotide variant TCGA : The Cancer Genome Atlas ToMMo : Tohoku Medical Megabank organization VAF : variant allele frequency [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03159572&atom=%2Fmedrxiv%2Fearly%2F2022%2F07%2F10%2F2022.07.06.22277241.atom