Identification and Characterization of Genomic Amplifications in Ovarian Serous Carcinoma
Abstract
This proposal is to apply genome-wide technologies to analyze ovarian cancer genome and transcriptome in parallel in the same ovarian tumors to reveal genes with concurrent genomic amplification and transcription upregulation. We propose to use digital karyotyping as the discovery tool to identify genomic amplification in ovarian carcinomas, and based on the results from 7 digital karyotyping libraries, we are able to identify several novel amplifications with high frequency as well as known amplified oncogenes including Cyclin E1, AKT2, LMyc. In the past year, we have focused on a novel amplicon located at chromosome 11q since it is frequently amplified in high-grade ovarian serous carcinomas. Combined genome and transcriptome analysis was performed at 48 tumors, and the results indicate Rsf-1 as the gene with most consistent DNA amplification as well as transcript and protein up-regulation. Furthermore, FISH analysis on a panel of ~110 ovarian carcinomas showed that patients with Rsf-1 amplification had significantly shorter overall survival that those without. The function of Rsf-1 in proliferation was also established by RNAi knock-down assays. Currently we are focusing on Rsf-1 and other candidate oncogenes identified by digital karyotyping to reveal their clinical and biological significance in ovarian carcinomas.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2006
- Accession Number
- ADA503268
Entities
People
- Tian-li Wang
Organizations
- Johns Hopkins University