Amplified Genes in Breast Cancer: Molecular Targets for Investigation and Therapy
Abstract
Our research focused on investigating acentric, autonomously replicating DNA containing amplified oncogenes (double minute chromosomes, DMs) as such structures occur in a significant fraction of human cancers. We proposed to develop methods to rapidly isolate and genotype DMs, to identify drugs to eliminate DMs, and to identify the mechanism(s) by which they are eliminated. We developed strategies to specifically tag DMs in living cells to enable analysis of their behavior during the cell cycle to enable us to ascertain differences between acentric structures and normal chromosomes to aid in the development of DM elimination reagents. We also devised and implemented novel cell labeling strategies to develop tumor models to determine how DM containing cells contribute to tumorigenesis, and to ascertain whether agents that effect DM elimination in vitro reduces tumor cell viability in vivo. Powerful new strategies and molecular tools were made available to the research community to enable sophisticated analyses of normal and abnormal chromosomes in cancer cells, and to allow studies of the relationship between genotype, phenotype and drug sensitivity in vivo.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1999
- Accession Number
- ADA382811
Entities
People
- Geoffrey M Wahl
Organizations
- Salk Institute for Biological Studies