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Role of Telomeres and Telomerase in the Pathogenesis of Human Cancer

William C. Hahn

From the Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA.

Address reprint requests to William C. Hahn, MD, PhD, Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115; email: William_Hahn{at}dfci.harvard.edu.

Specialized nucleoprotein structures, termed telomeres, cap the ends of human chromosomes. These terminal structures, composed of repetitive arrays of guanine-rich hexameric DNA together with specific telomere-binding proteins, play essential roles in protecting the chromosome from damage and degradation. In addition, several lines of evidence implicate telomere maintenance as an important regulator of cell life span. Activation of telomerase, a dedicated reverse transcriptase that synthesizes telomeric sequences, is strongly associated with cancer, and recent observations confirm that telomeres and telomerase perform important roles in both suppressing and facilitating malignant transformation. These dual functions of telomere biology are evident in the clinical manifestations of the multisystem syndrome, dyskeratosis congenita, forms of which display defects in telomerase function. Recent advances in our understanding of telomere biology indicate that the manipulation of telomeres and telomerase will lead to clinically significant applications in the diagnosis, prevention, and treatment of neoplastic disease.

Supported in part by grant no. K01 CA94223 from the United States National Cancer Institute, Bethesda, MD; the Doris Duke Charitable Foundation; a New Investigator Award (DAMD17-01-1-0049) from the United States Department of Defense; a Dunkin Donuts Rising Star Award; and a Research Award from the Association for the Cure of Cancer of the Prostate.

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