Prognostic Value of Telomere DNA Content in Invasive Breast Cancer
Abstract
Telomeres, which are specialized protein-nucleic acid complexes that protect the ends of chromosomes, are shortened each time a cell divides. Although the mechanisms that drive cancer initiation and progression are not known, genomic instability occurs in most tumors and is correlated with shortened telomeres. The loss of growth control in tumor cells results in excessive telomere shortening and, by extension, phenotypic variability. We hypothesized, therefore, that very short telomeres would facilitate progression to a metastatic phenotype and, therefore, that telomere DNA content (TC), a proxy for telomere length, would predict clinical outcome in breast cancer. Patient histories and tissues were obtained from the New Mexico Tumor Registry. TC was measured in 38 breast tumors and 38 paired specimens of tumor-associated, histologically-normal stroma. In tumor tissues, Kaplan-Meier analysis demonstrated that reduced TC was associated with disease recurrence or death and that high TC was associated with disease-free survival (p=O.00l). Unexpectedly, there was a similar association between TC and clinical outcome in the tumor-associated stroma (p.0.OOl). These findings show that TC in both breast tumors and tumor-associated, normal stroma predicts clinical outcome. This implies that telomere length is a characteristic of the cells' microenvironment, rather than a consequence of tumors' proliferation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2002
- Accession Number
- ADA407547
Entities
People
- Jeffrey K. Griffith
Organizations
- University of New Mexico