MITOCHONDRIAL GENOME ANALYSIS OF EPITHELIAL SEROUS OVARIAN CARCINOMA

描述（由申请人提供）：具有相似卵巢肿瘤特征的患者在病程和结局方面表现出异质性。虽然已经开发了许多治疗卵巢癌的方法，但我们仍然远远没有找到为什么卵巢癌患者在病程和结局方面表现出大量的异质性，这与疾病的种族差异有关。因此，需要更多的研究，不仅要了解卵巢癌细胞阶段颠覆的基本过程，以获得增殖优势，还要了解为什么卵巢癌患者在疾病的过程和结果中表现出大量的种族差异。在一生中ROS的积累和氧化性DNA损伤可能是有害的，并导致特定的线粒体基因组改变，可能参与卵巢癌的发展和进展。我们的中心假设是，浆液性卵巢癌组织中的线粒体DNA基因谱将识别组织学浆液性肿瘤阶段和高加索人和非裔美国人浆液性卵巢癌患者亚组中临床相关的突变和表达模式。具体目标是：（1）确定和评估mtDNA多态性/突变在非裔美国人和白人患者对浸润性上皮性浆液性卵巢癌易感性中的作用。(2)确定来自非洲裔美国人和高加索人的同一个体患者的浆液性卵巢肿瘤的“早期”阶段和正常周围卵巢组织之间的线粒体蛋白表达谱水平是否存在差异。在本申请中将进行多平台技术的组合，以准确评价上皮性浆液性卵巢癌亚型的遗传变化和类似疾病患者的亚类。这项研究的结果应该为开发适当的临床测试提供基础知识，以预测癌症患者的临床结果，这是有效治疗所需的。 公共卫生相关性：在具有看似相似属性的浆液性卵巢癌的过程和结果中观察到了大量差异，使得应用适当的治疗变得困难。描述组织学上皮性浆液性卵巢癌阶段和类似疾病患者（非洲裔美国人和高加索人）的亚分类中mtDNA基因的改变，应该更好地理解为什么这种疾病在非洲裔美国人中的死亡率高于高加索人。

DESCRIPTION (provided by applicant): Patients with similar ovarian tumor characteristics display heterogeneity in the course and outcome of the disease. While a number of treatment modalities have been developed for ovarian cancer, we still are far from finding why there are a great deal of heterogeneity show by ovarian cancer patients in the course and outcome regarding the disease racial differences. Therefore, more research is needed not only to understand the basic processes that are subverted by stages of ovarian cancer cells to gain a proliferative advantage, also why there are a great deal of racial differences show by ovarian cancer patients in the course and outcome of the disease. The accumulation of ROS and oxidative DNA damage during the course of a lifetime may be deleterious and lead to specific mitochondrial genome alterations that may be involved in the development and progression of ovarian cancer. Our central hypothesis is that mtDNA gene profiling in serous ovarian cancer tissues will identify clinically relevant patterns of mutations and expression in histological serous tumor stages and subgroups of Caucasian and African-American serous ovarian cancer bearing patients. Specific aims are: (1) To determine and evaluate the role of mtDNA polymorphism/mutations play between African American and Caucasian patients susceptibility to invasive epithelial serous ovarian cancer. (2) To determine whether there are differences in the level of mitochondrial protein expression profiles between "early" stages of serous ovarian tumors and normal surrounding ovarian tissue from same individual patient of African-American and Caucasian origin. A combination of multiplatform of technologies will be performed in this application to accurately evaluate genetic changes in epithelial serous ovarian cancer subtypes and sub-classification of patients with similar disease. Results from this study should provide basic knowledge to the development of proper clinical tests for prediction of cancer patients' clinical outcome which is required for efficacious therapies. PUBLIC HEALTH RELEVANCE: A great deal of differences has been observed in the course and outcome of serous ovarian cancer with seemingly similar attributes, making application of appropriate therapies difficult. Delineating the mtDNA gene alterations in histologic epithelial serous ovarian cancer stages and sub-classification of patients (African-American and Caucasian) with similar disease, should lead to better understanding why this disease has higher mortality rate in African American than in the Caucasian population.