MITOCHONDRIAL GENOME ANALYSIS OF EPITHELIAL SEROUS OVARIAN CARCINOMA

描述(申请人提供)：卵巢肿瘤特征相似的患者在疾病的过程和结果上表现出异质性。虽然已经开发了许多治疗卵巢癌的方法，但我们仍然远未发现为什么卵巢癌患者在疾病的过程和结果中表现出很大的异质性，因为疾病的种族差异。因此，不仅需要更多的研究来了解卵巢癌细胞为获得增殖优势而被不同阶段颠覆的基本过程，还需要更多的研究来了解为什么卵巢癌患者在疾病的过程和结果中表现出巨大的种族差异。一生中ROS的积累和DNA的氧化损伤可能是有害的，并导致特定的线粒体基因组改变，这可能参与卵巢癌的发生和发展。我们的中心假设是，浆液性卵巢癌组织中的mtDNA基因图谱将确定在组织学浆液性肿瘤分期和高加索人和非裔美国人浆液性卵巢癌患者亚群中临床相关的突变和表达模式。具体目的是：(1)确定和评估线粒体DNA多态/突变在非裔美国人和高加索人对浸润性上皮性浆液性卵巢癌易感性中的作用。(2)探讨早期浆液性卵巢肿瘤与同一个体非裔美国人和高加索人正常卵巢组织线粒体蛋白表达谱是否存在差异。在这项应用中，将执行多平台技术的组合，以准确评估上皮性浆液性卵巢癌亚型和类似疾病患者的亚型的基因变化。这项研究的结果应该为开发适当的临床测试以预测癌症患者的临床结果提供基础知识，这是有效治疗所必需的。 与公共卫生相关：在具有相似特征的浆液性卵巢癌的过程和结果中观察到了很大的差异，使得适当的治疗方法的应用变得困难。勾勒出组织学上皮浆液性卵巢癌分期中mtDNA基因的变化以及类似疾病患者(非裔美国人和高加索人)的亚型，将有助于更好地理解为什么非裔美国人的死亡率高于高加索人群。

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.