The Roles of Chromosome Breaks and Telomere Dynamics in the Genomic Instability Associated with Human Breast Cancer
Abstract
As part of their progression from normal to malignant cells, human tumors acquire a marked genomic instability, which is likely due in part to the progressive shortening and transient loss of telomeres from chromosome ends. Loss of telomeres allows chromosomes to fuse end-to-end, triggering chromosome fusion-bridge-breakage cycles that lead to genome rearrangements, loss of heterozygosity, and gene amplification. Our objective was to study the initial steps in this process using site-specific double strand breaks (DSBs) adjacent to interstitial telomere sequence (ITS) and a color-based detection system on a specially engineered chromosome. Over the course of this grant we have determined the inherent instability of ITS, shown that a DSB on the chromosome can lead to the seeding of new telomeres, defined the orientation of the APRT gene on the chromosome, identified chromosome loss as a problem, redesigned the test chromosome to avoid chromosome loss, constructed a new targeting vector, prepared an appropriate recipient cell line, developed the color-based detection system, and created a cell line carrying the redesigned chromosome. Characterization of the new cell line will set the stage for many of the experiments proposed in the original application; we will pursue those studies with funding currently being requested from other sources.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2000
- Accession Number
- ADA394777
Entities
People
- John H. Wilson
Organizations
- Baylor College of Medicine