Telomerase reverse transcriptase: prognostic and predictive molecular marker of glioma

Glioma is a group of tumors that arise from the glial cells in the brain. These cells support the function of the other main brain cell type—the neuron. Gliomas usually happen in the cerebral hemispheres of the brain, that controls many functions including movement, speech, thinking, and emotions. But they can also affect the brain stem, the lower part of the brain that controls functions like breathing, blood pressure, and heartbeat, the optic nerves, and cerebellum. Liquid biopsy offers a minimally invasive tool to diagnose and monitor the heterogeneous molecular landscape of tumors over time and therapy. Liquid biopsy is particularly challenging in brain tumors because mutant DNA is shed into the bloodstream at a much lower level than any other types of tumors.

Researchers led by Professor Bob Carter, MD, chief of neurosurgery and co-director of the Massachusetts General Hospital Brain Tumor Center developed an enhanced form of liquid biopsy that can detect and monitor genetic mutations that promote the growth of the most common type of adult brain tumors in blood samples. Their discovery which was published in the journal Clinical Cancer Research.

By comparing blood samples from patients with gliomas with tumor biopsy tissues from the same patients, the researchers found that a novel digital droplet polymerase chain reaction (ddPCR) blood test they pioneered could accurately detect and monitor two mutations of the gene TERT, C228T, and C250T, over time.

Telomerase reverse transcriptase (TERT) has received a great deal of attention in recent years for its role as a prognostic and predictive molecular marker of glioma. By ‘supercharging’ our ddPCR assay with novel technical improvements, the authors showed for the first time that the most prevalent mutation in malignant gliomas can be detected in blood, opening a new landscape for detection and monitoring of the tumors.

The researchers tested the performance of the ddPCR assay in tumor tissue and observed that the results aligned with the results from an independently performed clinical laboratory assessment of TERT mutations in the tumor specimens. Then they observed samples of blood plasma matched to patient tumors and found that the ddPCR assay could detect TERT mutations both in samples from MGH, as well as from similarly matched plasma and tumor samples from collaborators at other institutions.

The ddPCR assay has the ability to detect the presence of a glioma by 62.5%, which is an improvement over previous assays for TERT mutations in the blood for brain tumors, compared to the standard of tissue-based detection of TERT mutations.

The researchers look forward to expanding their assay to be able to differentiate many types of brain tumors. Their discovery has the potential to improve the diagnosis and monitoring of gliomas and may lead to future advancements in brain tumor diagnosis.