MITOCHONDRIAL GENOME ANALYSIS OF EPITHELIAL SEROUS OVARIAN CARCINOMA

上皮性浆液性卵巢癌的线粒体基因组分析

• 批准号: 7896248
• 负责人: Felix O Aikhionbare
• 金额: $ 5.8万
• 依托单位: MOREHOUSE SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7896248
• 关键词: Address; African American; Biological Models; Cancer Patient; Caucasians; Caucasoid Race; Characteristics; Classification; Clinical; Complex; Cystadenoma; Development; Diagnosis; Diagnostic; Diagnostic Neoplasm Staging; Disease; Disease Outcome; Epithelial; Epithelial Cells; Epithelial ovarian cancer; Gene Mutation; Genes; Genetic; Genetic Polymorphism; Goals; Heterogeneity; Histocompatibility Testing; Histologic; Human; Individual; Journals; Knowledge; Lead; Link; Malignant neoplasm of ovary; Minority; Mitochondria; Mitochondrial DNA; Mitochondrial Proteins; Modality; Molecular; Molecular Profiling; Mutation; Outcome; Ovarian; Ovarian Diseases; Ovarian Serous Adenocarcinoma; Ovarian Serous Tumor; Ovarian Tissue; Ovary; Oxidative Phosphorylation; Pathology; Patients; Pattern; Play; Population; Predictive Factor; Predisposition; Premalignant; Process; Protein Subunits; Reactive Oxygen Species; Reporting; Research; Role; Serous; Signal Transduction; Staging; Subgroup; Technology; Testing; Tissues; Tumor Subtype; Tumor stage; Two-Dimensional Gel Electrophoresis; Variant; Western Blotting; Woman; Work; adenoma; cancer cell; cancer therapy; carcinogenesis; clinically relevant; improved; mitochondrial DNA mutation; mitochondrial genome; mortality; outcome forecast; ovarian neoplasm; oxidative DNA damage; phrases; protein expression; public health relevance; racial difference; racial/ethnic difference; research study; tumor; tumor progression

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.

描述（由申请人提供）：具有相似卵巢肿瘤特征的患者在疾病的病程和结果上表现出异质性。尽管已经开发出多种针对卵巢癌的治疗方法，但我们仍然远远没有找到为什么卵巢癌患者在疾病的种族差异方面的病程和结果表现出很大的异质性。因此，需要更多的研究，不仅要了解卵巢癌细胞被不同阶段破坏以获得增殖优势的基本过程，还要了解为什么卵巢癌患者在病程和结果上表现出很大的种族差异。疾病。一生中ROS和氧化DNA损伤的积累可能是有害的，并导致特定的线粒体基因组改变，可能与卵巢癌的发生和进展有关。我们的中心假设是，浆液性卵巢癌组织中的 mtDNA 基因分析将识别白种人和非裔美国人浆液性卵巢癌患者的组织学浆液性肿瘤阶段和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侵袭性上皮浆液性卵巢癌易感性之间的作用。 (2) 确定来自非裔美国人和白种人的同一个体患者的浆液性卵巢肿瘤“早期”阶段和正常周围卵巢组织之间线粒体蛋白表达谱的水平是否存在差异。该应用将结合多平台技术来准确评估上皮性浆液性卵巢癌亚型的遗传变化以及类似疾病患者的亚分类。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，以预测有效治疗所需的癌症患者的临床结果。 公共健康相关性：浆液性卵巢癌的病程和结果存在很大差异，但具有看似相似的属性，因此难以应用适当的治疗方法。描述组织学上皮性浆液性卵巢癌分期和患有类似疾病的患者（非裔美国人和白种人）的亚分类中 mtDNA 基因的改变，应该可以更好地理解为什么这种疾病在非裔美国人中的死亡率高于白种人人群。