Epidemiology and Genomics of Ovarian Clear Cell Carcinoma

上皮性卵巢癌组织类型被认为有许多不同的遗传风险因素，体细胞 特征和临床结果。卵巢透明细胞癌(OCCC)是其较为罕见的组织类型之一。 约占诊断病例的7%。对于处于晚期的女性来说，这是非常重要的 致命性；肿瘤往往抵抗标准的铂类化疗药物。组织类型越常见， 高级别浆液性和子宫内膜样上皮性卵巢癌已被广泛研究，包括 通过大规模的努力，如癌症基因组图谱，确定基因组特征。小规模肿瘤剖面术 OCCC的研究表明，它与这些组织类型不同，OCCC的分子亚型是 很可能存在。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，目的是识别OCCC 可能导致靶向OCCC治疗的基因组特征是最优先考虑的。我们提出了一个 对OCCC患者的6项研究的探索性研究，包括靶向DNA测序、甲基化 分析，并结合转录和蛋白质组的表达分析。我们将确定哪些功能 大多数与OCCC患者的基线临床特征密切相关，如确诊时的年龄、肿瘤 分级、分期和临床结果，如总生存时间和疾病复发时间。至 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合作流行病学网络 代表最大的OCCC病例队列与相关的新鲜冰冻肿瘤标本和临床 注释。根据所获得的结果，我们将在一个独立的 近1000名OCCC患者。因为大多数被研究的患者都参加了病例对照研究， 包括种系基因分型和流行病学危险因素问卷，知识的财富有待于 收获是广泛的。这将使靶向疗法的发展取得实质性进展。 对抗这种罕见的、经常具有化疗耐药性的癌症，并很容易滋生更多的病因学、流行病学和 和临床OCCC研究。

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.