A NOVEL C-CIRCLE ASSAY FOR DETECTING ALTERNATIVE LENGTHENING OF TELOMERES (ALT) MECHANISMS

Low-grade gliomas, in particular astrocytoma, have been previously reported to harbor Alternative lengthening of telomere (ALT) to maintain their telomeres to aid sustained replication. Targeting genetic pathways specific to ALT mechanism is crucial in developing novel drugs to minimise recurrence and improve prognosis in low grade glioma patients. Herein, we used a novel C-circle assay to identify ALT positivity in a local, retrospective cohort of astrocytoma and oligodendroglioma, where matched primary and recurrent tumors were available. We identified a retrospective cohort of 25 patients with grade II or III astrocytomas (n=17) or oligodendrogliomas (n=8) where matched tissue from recurrences were available. DNA was extracted and a novel C-circle assay was used to determine the ALT status of the primary and recurrent tumors. Approximately 77% (13 out of 17) astrocytomas were positive for ALT. Only 25% (2 out of 8) oligodendrogliomas were ALT positive. LOH 1p/19q was confirmed in these cases. Patients who were ALT positive showed longer overall survival. We found a significant association with ALT and IDH1 mutation status and mutations in TP53. In conclusion, the C-circle assay provides a robust and quantitative measure of ALT and could be incorporated into routine clinical use.