Telomerase and Early Detection of Cancer: a National Cancer Institute Workshop

Extract

Cellular immortality is a hallmark of cancer. The recent identification of telomerase, an enzyme associated with cellular immortality, at multiple points along the continuum of multistep carcinogenesis has created considerable interest in its potential for the early detection of carcinogenesis ( 1 , 2 ) .

Telomerase is the enzyme that rebuilds telomeres, the TTAGGG-repeated ends of chromosomes. Germline cells express telomerase and are immortal. Although most fetal somatic cells express telomerase, the enzyme is considerably less active or inactive when the cells mature ( 3 ) . Thus, most somatic cells do not express telomerase and are mortal. Because of an end replication problem, i.e., incomplete synthesis of the lagging strand during DNA replication, the telomeres of mortal cells shorten with age and eventually reach a critical point at which chromosomal integrity is lost and proliferation ceases ( 1 ) . A rare somatic cell occasionally escapes programmed senescence by activating telomerase. The extended survival of such a cell could be conjectured to provide opportunities for the accumulation of additional genomic insults that might contribute to a progressive neoplastic evolution within that cell. If so, telomerase might serve as a key molecular marker of that process.