TELOMERES, TELOMERASE AND CANCER - IS THE MAGIC BULLET REAL

Nature recruited telomerase to compensate for the incomplete replicati on of chromosomal ends (telomeres). In higher organisms, telomeres are eroded at each cell division. Cancer cells frequently show chromosoma l instability resulting in ring chromosomes, telomeric associations, a nd dicentric chromosomes. As a consequence of telomeric erosion, the r ibonucleoprotein complex termed ''telomerase'' is reactivated in a sub population of cells. Telomerase adds a hexameric repeat of the sequenc e 5' TTAGGG 3' to the ends of the chromosomes and hence stabilizes the telomeric length. Telomerase is active in vertebrates mostly in germ cells and the early stage embryo but is inactivated or repressed in so matic cells. Detection of telomerase activity in the overwhelming majo rity of advanced and metastatic human cancers but not in most somatic cells implies that telomerase-dependent immortalization could contribu te to the malignancy. Future studies on the expression and regulation of the individual components of telomerase may enable us to clarify th e diagnostic and therapeutic potential of telomerase in cancer.