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。尽管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种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的临床过程的能力方面具有显著的局限性。这项建议的主要目的是产生最常见的卵巢癌组织学类型的综合分子谱，即，目的1.为寻找具有潜在临床意义的恶性肿瘤分子标志物提供依据。这些研究将特意集中在一种组织学类型上，以增加识别生物标志物的可能性，从而为新的和更具信息性的肿瘤分类方案奠定基础。在这些研究的过程中，一系列与卵巢癌生物学和肿瘤生物学相关的问题也将得到解决（目标2）。目标1：确定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不同亚组患者的分子标志物，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的患者。目标二：明确卵巢癌和其他常见肿瘤类型中蛋白质和基因表达模式的数据（结肠直肠癌和肺癌），以实现以下目标：1）确定浆液性卵巢癌与其他主要类型卵巢癌的基因/蛋白表达或基因组改变的特定模式（粘液性，类粘液性，和透明细胞）2）鉴定卵巢癌特有的标志物，可用于将其与正常卵巢组织以及其他原发部位的肿瘤区分开来（特别是结直肠癌和肺癌）3）鉴定卵巢、浆液性癌的新分子标记物，用其评估浆液性囊腺瘤和低恶性潜能的浆液性肿瘤作为候选浆液性癌前体病变。

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.