Telomere and Telomerase in Carcinogenesis: Their Role as Prognostic Biomarkers

Unlimited replicative potential is the hallmark of cancer cells. Telomere shortening, which occurs at each cell division, restricts cell proliferation in normal somatic cells. Maintenance of telomere length, required for the unlimited cell proliferation displayed by cancer cells, is provided by telomerase activity, expressed in the vast majority of tumors. Telomere/telomerase interplay has a critical role in tumor initiation and progression. Many tumor-based studies have demonstrated that neoplastic cells generally have shorter telomeres than their adjacent non-cancerous mucosa, strongly supporting the concept that telomere erosion is a critical event in carcinogenesis. Telomerase reverse transcriptase (TERT), the catalytic component of the telomerase complex, is usually absent in normal somatic cells but is expressed at variable levels in tumors. Specific mutations in its promoter may influence TERT levels. A body of data indicates that telomere length and levels of TERT/telomerase activity may be prognostic markers in cancers. Circulating cell-free TERT RNA may also be a promising marker for minimally invasive moni- toring of disease progression and response to therapy