Telomere Length and Genomic Stability as Indicators of Breast Cancer Risk
Annual summary 1 May 2001-30 Apr 2004
TEXAS UNIV SOUTHWESTERN MEDICAL SCHOOL AT DALLAS
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Telomeres are repetitive sequences that protect the ends of linear chromosomes and shorten during each cell division. Very short telomeres have been associated with changes in gene expression in yeast and decreased genome stability. We published the first proof that silencing effects can occur at human telomeres. A luciferase reporter near a telomere showed on average a 10-fold reduction in expression relative to internal control genes. The silencing is reversible through inhibition of hi stone deacetylases and dependent on telomere length. We further demonstrated spontaneously switch on and off of the telomeric genes, resulting in a second publication. We determined that a subset of short telomeres in human genome lead to replicative senescence aging and triggered early DNA damage-signaling pathways, resulting in a third publication. We developed and constructed both a 70-mer array and the combination of both fluorescence in situ hybridization technique and immunostaining, which can allow us detailed characterization of telomere lengths and specific gene rearrangements that will complement the expression data to create a detailed picture of the behavior of telomeres in the progression of breast cancer.
- Anatomy and Physiology
- Medicine and Medical Research