Defining microRNA Signatures for Early Detection in BRCA-Mutated Ovarian Cancer

描述（申请人提供）：由于卵巢癌的晚期诊断，其死亡率极高。表征早期前体病变和干细胞生态位的分子事件是在这些肿瘤的自然史中产生早期检测，化学预防和手术干预的新策略的第一步和必要步骤。因此，本研究旨在解决卵巢肿瘤发展的一个基本问题，即确定卵巢癌前体病变和肿瘤起始细胞的分子特征。为此，我们正在使用全基因组方法来确定非编码rna的表达，并将进一步确定它们在血清中的表达，以评估它们作为早期检测的生物标志物。这是第一次利用独特的小鼠卵巢癌模型来全面表征miRNA在肿瘤发展各个阶段的表达变化。该项目将对寻找新的分子途径进行早期诊断产生重大影响，这对降低疾病死亡率和化学预防至关重要。综上所述，本研究的成功完成不仅有助于更好的早期发现，而且有助于开发化学预防方法，这将对卵巢癌患者当前的预后产生重大影响。

DESCRIPTION (provided by applicant): Ovarian cancer has an extremely high mortality rate due it its late stage of diagnosis. Characterizing molecular events of the early precursor lesions and the stem cell niche is a first and necessary step to generating novel strategies for early detection, chemoprevention and surgical intervention in the natural history of these neoplasms. Hence, the proposed study aims at addressing a fundamental question in ovarian tumor development which is defining the molecular signature of precursor lesions and tumor initiating cells in ovarian cancer. Towards this, we are using genome-wide approaches to determine the expression of noncoding RNAs and will further determine their expression in serum in order to evaluate them as biomarkers for early detection. This is the first time that a unique murine model of ovarian cancer is being used to comprehensively characterize the changes in miRNA expression through various stages of tumor progression. This project will make a significant impact on identifying new molecular pathways for early diagnosis, which is critical in reducing the disease mortality and chemoprevention. In summary, successful completion of the proposed study would lead not only to better early detection but also development of chemopreventative methods, which could significantly impact the current prognosis of ovarian cancer patients.