Specificity and sensitivity of ALT-associated markers in cancer cells

Some tumors employ a mechanism called alternative lengthening of telomeres (ALT) to counteract telomere shortening-induced replicative senescence. Several hallmarks are used to identify cell lines and tumors as ALT-positive. Here, we analyzed a panel of ALT-positive and -negative cancer cell lines to investigate the specificity and sensibility of ALT-associated markers. We found that all the markers showed high sensitivity, indicating that cells not showing ALT markers are not ALT cells. Conversely, specificity varied significantly, i.e., many markers yield false positives. Detection of false positives may have influenced previous estimations of ALT incidence among tumors. Moreover, claims on the ‘coexistence’ of ALT and telomerase perhaps should be reconsidered. The findings prompt further study into the nature of these markers and their roles as either part of the ALT machinery or as by-products.