OVARIAN TUMOR PROJECT

这项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全面概况，以确定临床相关的分子肿瘤特征。尽管目前使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，但现有的方案在允许预测单个卵巢癌患者的临床病程方面有很大的局限性。这项建议的主要目的是建立最常见的卵巢癌组织类型的全面分子图谱，即严重癌，并为鉴定具有潜在临床相关性的严重癌的分子标志物提供基础(目标1)。这些研究将故意集中在一种组织类型上，以增加识别生物标记物的可能性，以此作为新的和更有信息量的肿瘤分类方案的基础。在这些研究过程中，还将讨论与卵巢癌生物学和一般肿瘤生物学有关的一系列相关问题(目标2)。目的1：明确250-300例浆液性卵巢癌的蛋白质和基因表达谱，以确定区分临床或生物学亚型的分子标记，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。目的：确定卵巢癌和其他常见肿瘤类型(结直肠癌和肺癌)的蛋白质和基因表达模式的数据，以追求以下目标：1)确定浆液性卵巢癌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)相比的基因/蛋白表达或基因组改变的特定模式；2)寻找卵巢癌特有的标志物，用于区分正常卵巢组织和其他原发部位的肿瘤(尤其是结直肠癌和肺癌)；3)寻找新的卵巢浆液性浆液性癌的分子标志物，用来评估浆液性囊腺瘤和低恶性潜能的浆液性肿瘤作为浆液性癌前病变的候选。

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.