Telomere dynamics, aging, and cancer: Study of human syndromes characteristic of premature aging

Age-related reduction of telomeric DNA sequences contributes to mitotic catastrophe and genetic instability, which in turn play major roles in the increased risk of developing cancer. Human B-cells from patients with Fanconi's anemia (FA), ataxia-telangiectasia (AT), Bloom syndrome (BS), and xeroderma pigmentosum (XP) syndromes, causing premature aging and predisposition to neoplasia, were studied for telomere dynamics and mitotic catastrophe, including the frequency of endoreduplication and structural abnormalities. We hypothesized that somatic cells affected by these syndromes have shortened telomeres and down-regulation of telomere repeat binding factor 2 (TRF2). Using conventional and molecular cytogenetic techniques such as quantitative fluorescence in situ hybridization (Q-FISH), we compared patients' cells to cells from age- and sex-matched individuals. The frequency of metaphases with mitotic catastrophe and telomeric associations was significantly higher in FA, BS, and AT cells than in controls, ...