Background: Ovarian cancer (OC) is a common and lethal gynaecologic malignancy. The prognosis of OC is variable among different patients treated with standard of care therapies. Herein, we described the mutational profiles of OC to identify underlying therapeutic targets and prognostic markers.
Methods: The study was performed on 38 Chinese patients with high-grade serous ovarian cancer (HGSOC). Most patients (86.8%) had advanced disease (stage III-IV). Tissue samples were subjected to capture-based targeted sequencing using a panel consisting of 520 cancer-related genes. Mutational profiles, including gene mutations and copy number variations (CNVs), were evaluated in each patient. Homologous recombination deficiency (HRD) status was also assessed. Analysis of the mutational profile with platinum-sensitivity, progression-free survival (PFS) and platinum-free interval (PFI) was performed.
Results: Germline BRCA1 and BRCA2 mutations were identified in 5 (13%) and 2 (5%) patients, respectively. Somatic genetic alterations were mainly identified in TP53 (97%), BRCA1 (24%), RB1 (21%), FGF23 (21%), CCND2 (18%), RECQL4 (18%) and NF1 (16%). CNVs were comprehensively distributed in 242 genes, with 76% (29/38) of patients harbouring at least one CNV. In addition to BRCA1, somatic genetic alterations were also present in other homologous recombination repair (HRR) genes, including CDK12 (5%), BRCA2 (3%), ATM (3%), BRIP1 (3%), CHEK1 (3%) and FANCI (3%). In total, 22 of 38 (58%) patients had genetic alterations in the HRR pathway.
The prognosis analysis indicated that BRCA1/2 mutations were significantly associated with improved PFI (p<0.05) and marginally associated with improved PFS (p=0.05). Patients with R0 resection found positive HRD showing a significant association with better PFI (p<0.05) and a marginal association with better PFS (p=0.06).
In patients with NF1 mutation, improved PFS and PFI were observed. However, the difference was not ideal (PFS, p=0.06, PFI, p=0.084). Platinum-sensitivity was significantly associated with BRCA1/2 mutations (p<0.01).
Conclusions: In OC patients, genetic mutations frequently occurred in both HRR and non-HRR genes. CNVs are widely present in many genes and patients. Mutational profiling also identified a number of potential therapeutic targets and prognostic markers at the molecular level that could contribute to the personalised treatment and management of OC.