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.
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