卵巢癌是全球致死率最高的妇科肿瘤，其5年生存率低于30%。目前卵巢癌的标准治疗依赖外科细胞减灭术联合辅助化疗。卵巢癌作为化疗敏感的实体瘤，临床上多通过铂类药物诱导细胞DNA发生双链断裂（DSB）杀伤肿瘤。其传统化疗初始响应率可达70%，但仍有半数患者在化疗后的两年内因产生化疗耐药的复发而死亡。同源重组（HDR）修复DSB是导致卵巢癌对顺铂等化疗耐药的关键分子通路。目前国际上对卵巢癌的个体化治疗仅关注于HDR通路的功能缺失性变异，但对HDR通路中的功能获得性变异尚无深入研究。本课题以肿瘤基因组图谱（TCGA）数据库为工具，发现HDR通路中上游基因NBN在卵巢癌组织中存在广泛的基因扩增，并可通过上调HDR通路对DSB的修复导致卵巢癌发生化疗耐药。故拟在实际临床样本中对上述基因扩增事件进行验证，研究其导致HDR上调的分子机制，并建立检测该基因扩增事件的方法，从而为卵巢癌的个体化医疗提供新的思路。

Ovarian cancer (OvCa), with a five-year survival rate less than 30%, is the most lethal gynecological tumor in the world. The general standard treatment of OvCa is characterized by debulking surgery and further chemotherapy. Seventy percent of the OvCa patients show desired response to chemotherapy at the initial of chemo administration. However, near half of those patients will develop chemo-resistant tumor relapse in the following two years and die from the recurrence. Homology-dependent recombination (HDR) pathway activation is crucial for the development of chemo-resistance in OvCa. Previous research projects mainly focus on the loss-of-function alteration events in the HDR pathway and identifying drug-sensitive subtypes of the disease. Nevertheless, the gain-of-function (GOF) genetic alterations in OvCa is still largely veiled. Our previous research identified copy number amplification of the NBN gene in HDR pathway as the most recurrent GOF DNA damage repair gene alteration in the OvCa tissues using The Cancer Genome Atlas (TCGA) database and validated the NBN amplification induced chemo-resistance phenotype in-vitro. In this study, we’ll evaluate the clinical significance of NBN amplification induced chemotherapy resistance, disclose the mechanism linking the genotype-phenotype bridge and develop a droplet digital PCR system to quantify the NBN amplification in the OvCa tissue for the prediction of chemo-resistant in the OvCa management.