OVARIAN TUMOR PROJECT

拟议研究的长期目标是利用现有技术生成卵巢癌分子改变的综合概况，以确定临床相关的分子肿瘤特征。虽然目前采用的基于形态学的卵巢肿瘤分类系统已经为将卵巢癌视为几个重叠但不同的疾病实体奠定了基础，但现有方案在预测个体卵巢癌患者临床病程方面存在显着局限性。该提案的主要目的是生成卵巢癌最常见的组织学类型，即严重癌的全面分子谱，并为鉴定具有潜在临床相关性的严重癌的分子标记提供基础（Aim 1）。这些研究将专注于一种组织学类型，以增加识别生物标志物的可能性，从而为新的和更有信息的肿瘤分类方案奠定基础。在这些研究过程中，一系列有关卵巢癌生物学和肿瘤生物学的相关问题也将得到解决（目标2）。目的1：确定250-300例浆液性卵巢癌的蛋白和基因表达谱，以确定区分临床或生物学上不同亚组患者的分子标记，包括早期与晚期疾病、低级别与高级别肿瘤以及生存与死亡患者。目的2：定义卵巢癌和其他常见肿瘤类型（结直肠癌和肺癌）中蛋白质和基因表达模式的数据，以实现以下目标：1)鉴定浆液性与其他主要类型卵巢癌（粘液性、子宫内膜样癌和透明细胞癌）的特异性基因/蛋白表达或基因组改变模式；2)鉴定卵巢癌特有的标志物，用于区分其与正常卵巢组织以及其他原发部位的肿瘤（特别是结直肠癌和肺癌）；浆液性癌用于评价浆液性囊腺瘤和低恶性潜能浆液性肿瘤作为浆液性癌前体病变的候选。

The long-term goal of the proposed studies is to exploit existing technologies to generate comprehensive profiles of molecular alteration in ovarian cancers in order to identify clinically relevant molecular tumor signatures. Although the currently employed morphology-based ovarian tumor classification system has laid the groundwork for viewing ovarian cancer as several overlapping, but distinct disease entities, the existing scheme has significant limitations in its ability to allow prediction of the clinical course of an individual ovarian cancer patient. The major thrust of this proposal is to generate comprehensive molecular profiles of the most common histologic type of ovarian carcinoma, i.e., serious carcinoma, and to provide a basis for the identification of molecular markers of serious carcinoma with potential clinical relevance (Aim 1). The studies will deliberately focus on one histologic type in order to increase the likelihood of identifying biomarkers on which to base new and more informative tumor classification schemes. In the course of these studies, a series of related questions pertaining to ovarian cancer biology and tumor biology in general, will also be addressed (Aim 2). Aim 1: To define protein and gene expression profiles in 250-300 serous ovarian carcinomas, in order to identify molecular markers that distinguish clinically or biologically distinct subgroups of patients, including those with early versus advanced stage disease, low versus high grade tumors, and those with survival versus death. Aim 2: To define data on protein and gene expression patterns in ovarian carcinomas and other common tumor types (colorectal and lung carcinomas) to pursue the following objectives: 1) To identify specific patterns of gene/protein expression or genomic alteration that characterize serous versus other major types of ovarian carcinoma (mucinous, endometrioid, and clear cell) 2) To identify markers unique to ovarian carcinomas that can be used to distinguish them from normal ovarian tissues as well as tumors from other primary sites (specifically colorectal and lung cancers) 3) To identify novel molecular markers of ovarian, serous carcinomas with which to evaluate serous cystadenomas and serous tumors of low malignant potential as candidate serous carcinoma precursor lesions.