Epigenetic Characterization of Ovarian Cancer
Abstract
The purpose of this research project is to identify genes that are hypermethylated in epithelial ovarian cancers on a genome-wide scale and determine if this is histology-specific. The approach is to use normal ovarian surface epithelium (NOSE) and malignant cells obtained directly from surgically removed specimens in order to most closely approximate the methylation status in vivo. Cultured cells are mock treated, or treated with 5-AzaC, a potent DNA methyltransferase inhibitor, followed by microarray analysis to identify genes that exhibit increased expression in response to drug treatment. The methylation status will be confirmed in the original tumor and assessed in a large panel of ovarian cancer specimens to determine prevalence of aberrant methylation. We will analyze five cancers each of serous, endometrioid, mucinous and clear cell histologies, along with five NOSE specimens. We have developed protocols for culture and 5-AzaC treatment of normal and malignant ovarian cells and criteria (e.g., >or= 90% epithelial, RNA quality) for microarray analysis. We have accrued 13 malignant samples (3 serous already arrayed, 1 serous and 1 endometrioid pending) and 19 NOSE specimens (9 that meet our criteria). Because of small cell numbers, NOSE specimens will be pooled for array hybridization. Collection of cancer and NOSE samples is ongoing, and analysis of candidate genes will begin once we obtain initial array results for the pooled NOSE controls.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2005
- Accession Number
- ADA452440
Entities
People
- Susan K. Murphy
Organizations
- Duke University Hospital