Abstract
BACKGROUND: Studies on the prevalence of BRCA1/2 mutations in ovarian cancer mainly focused on germline single-nucleotide variant (SNV)/insertion/deletion (indel). The status of large genomic rearrangement (LRG) and somatic mutation were poorly investigated. METHODS: Paired blood and tumor DNA from an unselected cohort of 115 Chinese high grade serous ovarian cancer (HGSOC) patients were collected and analyzed for BRCA1/2 SNV and indel by NGS. BRCA1/2 LRG was detected by MLPA. Clinicopathological characteristics including age at diagnosis, FIGO stage, family history and follow-up data were collected for further analysis. RESULTS: A total of 115 HGSOC patients were screened. Among them, 30 (26.1%) had germline BRCA1/2 mutations, including 19 (16.5%) SNV/indels, 5 (4.3%) LGRs in BRCA1, and 6 (5.2%) SNV/indels in BRCA2. Ten (8.7%) had somatic BRCA1/2 mutations, including 5 (4.3%) in BRCA1 and 5 (4.3%) in BRCA2. The entire tumor BRCA1/2 mutation frequency was 34.8%. No patients were found with two or more deleterious BRCA1/2 mutations. The proportion of germline (66.7%) and tumor (75%) mutation carriers was significantly increased for patients with family history when compared with those without (P<0.05). Patients with germline BRCA1/2 mutation appeared to be younger than non-carriers (mean age, 50.9 vs. 54.4 years, P=0.004) and somatic mutation carriers (mean age, 50.9 vs. 58.7 years, P=0.009). No significant association was found between BRCA1/2 status and clinicopathological characteristics including stage and family history of other cancer than breast and ovarian cancer. In univariate and Cox regression analysis, patients with tumor BRCA1/2 mutations had significant improvements than non-carriers in overall survival in the first two years after surgery (P<0.05). No significant impacts were found between various mutation status in PFS. CONCLUSIONS: There is a high germline and tumor BRCA1/2 mutation incidences in Chinese HGSOC patients. Germline mutations were associated with family history and age at diagnosis, whereas somatic mutations were not. In our study, tumor BRCA1/2 mutations showed a time-depended improved survival outcome. A larger cohort should be examined to clarify the relation between BRCA1/2 mutation and survival outcomes.