ALTERNATIVE LENGTHENING OF TELOMERES
Telomeric C-Circle DNA specific to the ALT mechanism was discovered, enabling the first quantitative test for ALT activity. C-Circles are partially single-stranded telomeric (CCCTAA)n DNA circles that are present in 1000-fold greater abundance in ALT[+] cells than ALT[-] cells (telomerase[+] or normal somatic cells). It is the only assay for ALT that is rapidly and linearly responsive to changes in ALT activity and hence the only assay that can be used to screen for ALT inhibitors or generally measure changes in ALT activity.
The C-Circle assay has opened up a range of opportunities for ALT research and the clinical detection of cancers that rely on the ALT mechanism. CBI has successfully applied qPCR to the detection of ALT activity (CC-ALT qPCR) by measuring both telomere content and telomeric C-Circle DNA that is specific for ALT. Sensitivity of our qPCR-ALT assay is >25 times higher than in a standard radioisotope dot blot hybridization assay.