Can a Blood Test Accurately Detect Mutations that Lead to Brain Cancer?

A team of researchers at Massachusetts General Hospital have developed an enhanced form of liquid biopsy that that accurately detect and monitor mutations that promote the development of gliomas, the most common type of adult brain tumor.

The novel digital droplet polymerase chain reaction (ddPCR) blood test can accurately detect and monitor two mutations of the gene TERT, labeled C228T and C250T, which are present in more than 60% of all gliomas, and in 80% of all aggressive high-grade gliomas. Liquid biopsy detects cancer by detecting fragments of tumor DNA in blood circulation. Until now, the nature of brain tumors made them difficult to detect using this technique.

“Liquid biopsy is particularly challenging in brain tumors because mutant DNA is shed into the bloodstream at much lower level than any other types of tumors,” Leonora Balaj, PhD, a member of the research team, said in a press release. “By ‘supercharging’ our ddPCR assay with novel technical improvements, we 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.”

In a test of tumor tissue, the ddPCR assay was found to have perfect concordance with independently performed laboratory assessment of TERT mutations in the specimens (95% CI, 94%-100%). The team followed up by using the test to analyze blood plasma samples matched to patient tumors and again found that the assay could detect TERT mutations in both discovery and blinded multi-institution validation cohorts. In plasma detection, the test has an overall sensitivity of 62.5% (95% CI, 52%-73%) and a specificity of 90% (95% CI, 80%-96%) compared to standard tissue-based detection of TERT mutations.

Data from the ddPCR testing has been published in Clinical Cancer Research.