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.
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