Abstract 141P
Background
Ovarian cancer (OC) is one of the leading causes of cancer-related deaths in women both in Asia and worldwide. The NCCN guidelines suggest all newly diagnosed OC patients should take genetic risk evaluation including BRCA1/2 testing. OC patients who have deleterious BRCA1/2 variants are likely to benefit from PARP inhibitors. We aimed to investigate the prevalence and characteristics of BRCA1/2 mutations in Chinese OC patients.
Methods
Next-generation sequencing targeting 450 cancer genes was performed on formalin-fixed, paraffin-embedded (FFPE) tumor tissues and matching blood samples collected from a cohort of 245 Chinese OC patients. Genomic alterations included single base substitution (SNV), short and long insertion/deletion (Indel), copy number variation, gene fusion and rearrangement.
Results
BRCA1/2 mutations were detected in 29% (71/245) of patients with OC, 22 (9%) patients harbored somatic mutations, 51 (20.8%) patients harbored germline mutations, and 2 (0.8%) patients harbored both somatic and germline mutations. Notably, 18.8% of patients without a family history of HBOC syndrome were found to carry gBRCA mutations. Among patients with BRCA1/2 mutations, 71.8% harbored BRCA1 mutations, 31% harbored BRCA2 mutations, respectively. 67.6% of the patients were diagnosed with high-grade serous subtype. 87.3% of the patients were diagnosed with FIGO stage III/IV disease. In all classes of variants, SNVs and short Indels (90.1%) were the most common variant types of BRCA1/2, while the percentages of gene rearrangements/fusions and long Indels were 5.6% and 4.2%, respectively. In addition, the mutation sites were distributed in the full length of BRCA1/2 genes and no hotspot was observed.
Conclusions
Our data revealed that BRCA1/2 mutations occurred in 29% of Chinese OCs, consistent with the population data analysis of PAOLA-1 study (29%). The patients with BRCA1/2 mutations had a higher percentage of late-stage disease and high-grade serous subtype. In addition, 18.8% of the patients without family history were found to carry gBRCA mutations, which support that all OC patients should be tested for BRCA1/2 mutations for a better treatment decision, in China.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Shandong Provincial Hospital Affiliated to Shandong First Medical University.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.