OBJECTIVE: To define genetic profiling of homologous recombination (HR) deficiency in Chinese ovarian cancer patients.
METHODS: we have applied next-generation sequencing to detect deleterious mutations through all exons in 31 core HR genes. Paired whole blood and frozen tumor samples from 50 Chinese women diagnosed with epithelial ovarian carcinomas were tested to identify both germline and somatic variants.
RESULTS: Deleterious germline HR-mutations were identified in 36% of the ovarian cancer patients. Another 5 patients had only somatic mutations. BRCA2 was most frequently mutated. Three out of the 5 somatic mutations were in RAD genes and a wider distribution of other HR genes was involved in non-serous carcinomas. BRCA1/2-mutation carriers had favorable platinum sensitivity (relative risk, 1.57, p<0.05), resulting in a 100% remission probability and survival rate. In contrast, mutations in other HR genes predicted poor prognosis. However, multivariate analysis demonstrated that platinum sensitivity and optimal cytoreduction were the independent impact factors influencing survival (hazards ratio, 0.053) and relapse (hazards ratio, 0.247), respectively.
CONCLUSIONS: our results suggest that a more comprehensive profiling of HR defect than merely BRCA1/2 could help elucidate tumor heterogeneity and lead to better stratification of ovarian cancer patients for individualized clinical management.

In the present study, the role of lncRNAs in response to radiation-induced DNA damage and oxidative stress were explored to improve our understanding of the biological pathways activated upon radiation-induced toxicity. The toxicity of X-ray radiation on human bronchial epithelial cell lines (HBE) was determined through a dose-dependent increase in ROS production and γ-H2AX formation and changes to lncRNA expression was observed and quantified using lncRNA-specific microarrays. 115 lncRNAs expression was increased in a dose-dependent manner following X-ray irradiation. Bioinformatic prediction algorithms determined that these lncRNAs significantly affect the p53 signaling pathway, and, more specifically, the BRCA 1 transcription factor and coding genes adjacent to BRCA 1. Our results highlight a previously uncharacterized role for lncRNAs to act via the p53-pathway in response to X-ray-induced DNA damage, and suggest lncRNAs may serve as novel indicators for radiation toxicity.