Characterizing Molecular Subtypes of Ovarian Cancer in African-American Women

非裔美国女性卵巢癌分子亚型特征

• 批准号: 9386358
• 负责人: Jennifer A. Doherty
• 金额: $ 55.57万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-10-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9386358
• 关键词: Accounting; African American; Age; American; Anatomy; Behavior; Cancer Etiology; Cessation of life; Clinical; Data; Databases; Development; Disease; Enrollment; Epidemiologic Studies; Epidemiology; Epithelial ovarian cancer; Epithelium; Etiology; European; Evolution; Formalin; Frequencies; Future; Gene Expression; Gene Expression Profile; Gene Mutation; Genetic; Health Services Accessibility; Histologic; Incidence; Individual; Investigation; Malignant Neoplasms; Malignant neoplasm of ovary; Medical Genetics; Molecular; Molecular Profiling; Mutation; Newly Diagnosed; Ovarian; Ovarian Tissue; Paraffin Embedding; Participant; Pathway interactions; Pattern; Play; Population; Race; Reporting; Research; Resources; Sampling; Serous; Site; Socioeconomic Factors; Staging; Surface; The Cancer Genome Atlas; United States; Woman; Work; base; cancer epidemiology; cancer gene expression; cancer risk; cancer subtypes; cancer survival; cancer type; comparative; epidemiology study; exome sequencing; infancy; mRNA Expression; malignant breast neoplasm; molecular subtypes; mortality; outcome forecast; ovarian neoplasm; peripheral blood; population based; protein expression; public health relevance; socioeconomics; survival prediction; targeted treatment; therapeutic development; therapeutic target; transcriptome; tumor

 DESCRIPTION (provided by applicant): Epithelial ovarian cancer (EOC) accounts for 5% of malignancies and while it is the eighth most common cancer in US women, it is the fifth leading cause of cancer deaths. It is now considered not as a single disease, but rather as a diverse group of tumors with distinct origins, histotypes, mutation profiles, protein and gene expression profiles, and prognosis. Over 75% of EOC is high-grade serous (HGSC), accounting for 90% of disease-specific mortality. Systematic molecular characterization of HGSC by the Cancer Genome Atlas (TCGA) and others has demonstrated robust gene expression subtypes of HGSC. HGSC subtypes have been studied almost exclusively in individuals of European ancestry, and it is thus unknown whether these or other subtypes exist in populations with different genetic backgrounds and exposures. Indeed five-year relative survival from EOC is only 36.4% for African American (AA) women, compared to 44.3% for European American (EA) women. For breast cancer, aggressive subtypes are more common among AA women than EA women, and this partially explains survival differences. It is possible that aggressive subtypes of HGSC are overrepresented in AA women, but analogous research in EOC is in its infancy because it is one ninth as common as breast cancer, and molecular subtypes have only recently been identified. The African American Cancer Epidemiology Study (AACES) is an ongoing multi-site population-based study which will ultimately include 850 AA women with newly diagnosed EOC and their age-matched controls. This study will examine socioeconomic, epidemiologic, genetic and clinical factors and ovarian cancer risk and survival. As the only epidemiologic study of EOC in AA women to date, it provides a rich resource to examine molecular features of this disease. For 300 AACES participants, we propose to generate whole transcriptome data from their formalin-fixed paraffin-embedded HGSC ovarian tumors and exome sequencing data from these tumors and corresponding peripheral blood to: determine gene expression-based, and mutation-based, subtypes of HGSC tumors in AA women, compare the relative frequencies of subtypes in AA and EA populations, and evaluate whether subtype-specific survival differs by population; and characterize similarities and differences in gene expression patterns and mutational spectra across each of the molecular subtypes in AA and EA women to define key subtype-specific and population-specific pathways. The results from this study will provide key information to understand survival differences in AA women, and will more precisely define molecular subtypes allowing for future functional characterization and therapeutic development.

 描述（由申请人提供）：上皮性卵巢癌（EOC）占恶性肿瘤的5%，虽然它是美国女性第八大最常见的癌症，但它是癌症死亡的第五大原因。它现在被认为不是一种单一的疾病，而是一组不同的肿瘤，具有不同的起源，组织型，突变谱，蛋白质和基因表达谱以及预后。超过75%的EOC是高级别浆液性（HGSC），占疾病特异性死亡率的90%。通过癌症基因组图谱（TCGA）和其他方法对HGSC进行的系统性分子表征已经证明了HGSC的稳健的基因表达亚型。HGSC亚型几乎只在欧洲血统的个体中进行了研究，因此不知道这些或其他亚型是否存在于具有不同遗传背景和暴露的人群中。事实上，非裔美国人（AA）女性的EOC五年相对生存率仅为36.4%，而欧洲裔美国人（EA）女性为44.3%。对于乳腺癌，侵袭性亚型在AA女性中比EA女性更常见，这部分解释了生存差异。有可能是那些具有攻击性的 HGSC在AA女性中的比例过高，但EOC的类似研究仍处于起步阶段，因为它是乳腺癌的九分之一，并且分子亚型最近才被确定。的 非裔美国人癌症流行病学研究（AACES）是一项正在进行的多中心人群研究，最终将纳入850名新诊断EOC的AA女性及其年龄匹配的对照组。这项研究将探讨社会经济，流行病学，遗传和临床因素和卵巢癌的风险和生存。作为迄今为止唯一的AA女性EOC流行病学研究，它提供了丰富的资源来检查这种疾病的分子特征。对于300名AACES参与者，我们建议从他们的福尔马林固定石蜡包埋的HGSC卵巢肿瘤中生成全转录组数据，并从这些肿瘤和相应的外周血中生成外显子组测序数据，以确定AA女性中基于基因表达和基于突变的HGSC肿瘤亚型，比较AA和EA人群中亚型的相对频率，并评估亚型特异性生存率是否因人群而异;并描述AA和EA女性中每个分子亚型的基因表达模式和突变谱的相似性和差异，以定义关键的亚型特异性和人群特异性途径。这项研究的结果将为了解AA女性的生存差异提供关键信息，并将更精确地定义分子亚型，以便于未来的功能表征和治疗开发。