Telomerase Independent Telomere Maintenance in Ovarian Cancer: A Molecular Genetic Analysis
Abstract
The goal of this project is to elucidate some of the genetic and biological determinants of ovarian cancer, focusing on an in vitro model for ovarian cancer that we have developed. We found that immortalization and transformation of human ovarian surface epithelial (HOSE) cells can differ in the pathway used for telomere length maintenance, a phenomenon that we have also observed in the clinical disease. We have found that the majority of our HOSE cell cultures use the Alternative Lengthing of Telomeres (ALT) pathway for telomere maintenance, thereby providing an in vitro model to characterize the underlying basis of the ALT pathway in ovarian cancer. During this year of funding we have completed characterization of 50 ovarian tumors and found two that are telomerase negative and contain the characteristic long telomeres associated with the ALT pathway. We have also developed and optimized the technique to detect ALT- associated PML nuclear bodies in paraffin embedded tissues. This technology may distinguish additional ALT tumors among the cohort of telomerase negative tumors so far identified. Finally, we have improved our ability to profile RNA from these tumors by establishing and optimizing several technical aspects including isolation of RNA from microdissected tissue. The techniques developed in the last year will be critical in assessing expression patterns of ovarian tumors that use ALT for telomere maintenance.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2003
- Accession Number
- ADA420861
Entities
People
- Dominique Broccoli
Organizations
- Fox Chase Cancer Center