e17525 Background: Ovarian cancer (OC) is a common and lethal gynecologic malignancy. The prognosis of OC is variable among different patients treated with standard of care therapies. Herein, we described mutational profiles of OC to identify underlying therapeutic targets and prognostic markers. Methods: The study was performed in 38 Chinese patients with high-grade serous ovarian cancer (HGSC), the most common subtype of OC. 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 mutational profile with platinum-sensitivity, progression-free survival (PFS) and platinum-free interval (PFI) were performed. Results: 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 harboring at least one CNV. In addition to BRCA1, genetic alterations were also presented in other homologous recombination repair (HRR) genes including CDK12 (5%), BRCA2 (3%), ATM (3%), BRIP1 (3%), CHEK1 (3%) and FANCI (3%). There were 22 of 38 (58%) patients with genetic alterations of the HRR pathway. In the study, 28 patients were platinum-sensitive (74%) and 10 were platinum-resistant (26%). Platinum-sensitivity was significantly associated with BRCA1/2 mutations (p < 0.01). In platinum-resistant patients, 7 of 10 patients harbored genetic alterations of actionable therapeutic targets such as PIK3CA, TSC1 and HER2 alterations. 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). Although no association was observed between HRD status and patient prognosis, subgroup analysis in patients with R0 resection found positive HRD showing significant association with better PFI (p < 0.05) and marginal association with better PFS (p = 0.06). Further analysis of HRD classified by NF1 revealed different PFS and PFI among patients harboring positive HRD, negative HRD with NF1 mutations and negative HRD with wild type NF1 (p < 0.05). The study also observed association of LRP1B mutations and RAD52 amplification with worse PFS (p < 0.05). Conclusions: In OC patients, genetic mutations were frequently occurred in both HRR and non HRR genes. CNVs were widely presented in many genes and patients. The mutational profiling also identified a number of potential therapeutic targets and prognostic markers at molecular level which could contribute to personalized treatment and management of OC.
Neurotrophin receptors- prognostic markers and therapeutic targets for HNSCC?
