Journal Article

Homologous recombination inquiry through ovarian malignancy investigations: JGOG3025 Study

Sugiyama, Toru, Kajiyama, Hiroaki, Baba, Tsukasa, Okamoto, Aikou, Enomoto, Takayuki, Yoshihara, Kosuke, Yoshida, Hiroshi, Nishino, Koji, Kagimura, Tatsuo, Shimada, Muneaki, Oda, Katsutoshi, Sekine, Masayuki, Takamatsu, Shiro, Matsumura, Noriomi, Yaegashi, Nobuo, Tokunaga, Hideki, Sasajima, Yuko

2023

Overview

The Cancer Genome Atlas (TCGA) network has clarified that ~50% of high‐grade serous ovarian cancers show homologous recombination deficiency (HRD). However, the frequency of HRD in Japanese patients with ovarian cancer remains unclear. We aimed to identify the frequency of HR‐associated gene mutations 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 according to the criteria. We used frozen tumor tissues to extract DNA and performed next‐generation sequencing for 51 targeted genes (including 29 HR‐associated genes) in 701 ovarian cancers (298 high‐grade serous cases, 189 clear cell cases, 135 endometrioid cases, 12 mucinous cases, 3 low‐grade serous cases, 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 mutations were 45.2% (317/701) and 18.5% (130/701), respectively, in the full analysis set. 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 adjusted hazard ratios of 0.72 (95% CI, 0.55–0.94) and 0.57 (95% CI, 0.38–0.86) for PFS and OS, respectively, compared with those without HRD (p = 0.016 and 0.007). Our study demonstrated that mutations in HR‐associated genes were associated with prognosis. Further studies are needed to investigate the prognostic impact of each HR‐associated gene in ovarian cancer. Ovarian cancers with HR‐associated gene mutations show platinum sensitivity, leading to better outcomes. In particular, advanced‐stage clear cell carcinoma harboring HR‐associated gene mutations demonstrated longer PFS and OS.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: BRCA1 protein / Chemotherapy / Clinical outcomes / Clinical significance / Collaboration / DNA methylation / DNA sequencing / Enrollments / Fallopian tubes / Genes / Genomes / HITOMI study / Homologous recombination / homologous recombination deficiency / Informed consent / JGOG3025 / Malignancy / Mutation / Next-generation sequencing / Observational studies / Oncology / Original / ORIGINAL ARTICLES / Ovarian cancer / Patients / Surgery / targeted sequencing panel / Tumors