Epidemiology and Genomics of Ovarian Clear Cell Carcinoma

卵巢透明细胞癌的流行病学和基因组学

• 批准号: 9597497
• 负责人: ELLEN L. GOODE
• 金额: $ 20.75万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9597497
• 关键词: Age; Area; Biological; Biology; Bypass; Cancer Patient; Candidate Disease Gene; Case-Control Studies; Characteristics; Clinical; Clinical Data; Clinical Research; Collection; DNA; DNA Methylation; DNA analysis; DNA sequencing; Databases; Development; Diagnosis; Diagnostic; Disease; Enrollment; Epidemiologic Methods; Epidemiology; Epigenetic Process; Epithelial ovarian cancer; Etiology; Fostering; Freezing; Frequencies; Future; Gene Expression Profile; Genes; Genetic; Genomics; Genotype; Goals; Grant; Inherited; Investigation; Knowledge; Lead; Malignant Neoplasms; Methylation; Molecular; Observational Study; Outcome; Ovarian Clear Cell Tumor; PIK3CA gene; Patients; Pharmacotherapy; Platinum; Proteomics; Questionnaires; Recurrence; Research; Research Design; Research Personnel; Resistance; Resources; Risk Factors; Serous; Solid; Somatic Mutation; Specimen; Standardization; TP53 gene; Technology; The Cancer Genome Atlas; Therapeutic; Time; Woman; Work; base; cancer epidemiology; cancer genome; cancer genomics; clinically relevant; cohort; disorder subtype; epidemiology study; epigenomics; follow-up; improved; molecular subtypes; next generation; novel strategies; response; survival outcome; targeted treatment; transcriptomics; tumor

Epithelial ovarian cancer histotypes are thought to have numerous distinct inherited risk factors, somatic features, and clinical outcomes. Ovarian clear cell carcinoma (OCCC) is one of its rarer histotypes, representing approximately seven percent of diagnoses. For women presenting at advanced stage, it is highly lethal; the tumor tends to resist standard platinum-based chemotherapeutics. The more common histotypes, high-grade serous and endometrioid epithelial ovarian cancer, have been extensively studied including genomic characterization by large-scale efforts such as The Cancer Genome Atlas. Small-scale tumor profiling studies in OCCC suggest that it is distinct from these histotypes and that molecular subtypes of OCCC are likely to exist. Therefore, as the majority of findings from The Cancer Genome Atlas project are not expected to be applicable to OCCC, improving our understanding of the biology of OCCC with the goal of identifying genomic features which may lead to targeted OCCC therapeutics is of highest priority. We propose an exploratory study of OCCC patients from six studies, including targeting DNA sequencing, methylation profiling, and combined transcriptomic and proteomic expression analyses. We will identify which features most strongly associate with the baseline clinical features of OCCC patients, such as age at diagnosis, tumor grade, and stage, and with clinical outcomes, such as overall survival time and time to disease recurrence. To accomplish our aims, we will establish a collaborative epidemiologic network including investigators of studies representing the largest cohorts of OCCC cases with associated fresh frozen tumor specimens and clinical annotation. Based on the results obtained, we will conduct targeted follow-up in an independent collection of nearly 1,000 OCCC patients. As the majority of studied patients were enrolled into case-control studies which included germline genotyping and epidemiologic risk factor questionnaires, the wealth of knowledge to be gained is extensive. This will enable substantial progress towards the development of targeting therapeutics against this rare, frequently chemo-resistant cancer and will readily foster additional etiologic, epidemiologic, and clinical OCCC research.

上皮性卵巢癌组织型被认为具有许多不同的遗传风险因素， 特征和临床结果。卵巢透明细胞癌（OCCC）是其较罕见的组织型之一， 占诊断总数的7%。对于处于晚期的女性来说， 致命的;肿瘤倾向于抵抗标准的基于铂的化疗药物。更常见的组织型， 高级别浆液性和类浆液性上皮性卵巢癌，已被广泛研究，包括 通过癌症基因组图谱等大规模工作进行基因组表征。小规模肿瘤分析 对OCCC的研究表明，它不同于这些组织型，OCCC的分子亚型是 可能存在。因此，由于癌症基因组图谱项目的大多数发现预计不会 适用于OCCC，提高我们对OCCC生物学的理解， 可以导致靶向OCCC治疗的基因组特征具有最高优先级。我们提出了一个 OCCC患者的探索性研究来自六项研究，包括靶向DNA测序、甲基化 谱分析和组合的转录组学和蛋白质组学表达分析。我们将确定哪些特征 与OCCC患者的基线临床特征（如诊断时的年龄、肿瘤大小）相关性最强 分级和分期，以及临床结果，如总生存时间和疾病复发时间。到 为了实现我们的目标，我们将建立一个包括研究人员在内的流行病学合作网络。 代表最大的OCCC病例队列，具有相关的新鲜冷冻肿瘤标本和临床 注释。根据获得的结果，我们将在一个独立的收集， 近千名OCCC患者由于大多数研究的患者都参加了病例对照研究， 包括生殖系基因分型和流行病学危险因素问卷， 收获是广泛的。这将使靶向治疗的发展取得实质性进展 针对这种罕见的，经常化疗耐药的癌症，并将很容易促进额外的病因学，流行病学， 临床OCCC研究。