Breakthrough assay a ‘tenfold improvement over any prior assay for TERT mutations in the blood for brain tumors,’ MGH says in an affirmation of a diagnostic technology clinical labs might soon use

In recent years, investors have poured tens of millions of dollars into companies that promised to create non-invasive cancer tests which use liquid biopsy technology. Medical laboratory scientists even watched some of these companies hype their particular liquid biopsy tests before clinical studies generated data demonstrating that these tests produced accurate, reliable, and reproducible results.

For diagnosing cancer, a liquid biopsy test typically uses a blood sample with the goal of finding and identifying circulating tumor cells. Harvard Medical School researchers at Massachusetts General Hospital (MGH) believe they have developed just such a blood test. Their assay utilizes an enhanced form of liquid biopsy to detect and monitor one of the more prevalent types of brain tumor in adults—a glioma—and, according to a Harvard news release, can detect the presence of glioma at a significantly higher “overall sensitivity” than other similar liquid-biopsy tests.

Gliomas start in glia cells contained in the brain or spine. They account for about 30% of all brain and central nervous system tumors and 80% of all malignant brain tumors.

During their study, MGH researchers compared blood samples and tumor biopsy tissues from patients diagnosed with a glioma. They discovered that an assay they developed—a droplet digital polymerase chain reaction (ddPCR) blood test—could detect and monitor two types of telomerase reverse transcriptase (TERT) promoter gene mutations—C228T and C250T. These two gene mutations promote cancer growth and are present in more than 60% of all gliomas. The mutations are also present in 80% of all high-grade gliomas, which are the most aggressive and life-threatening types of the cancer.  

In the press release, instructor in Neurosurgery at MGH and one of the study’s authors, Leonora Balaj, PhD, said, “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.”

The MGH researchers released their findings in Clinical Cancer Research, a peer-reviewed medical journal devoted to the field of oncology published by the American Association of Cancer Research (AACR). 

Bob Carter, MD, PhD (above), is neurosurgical oncologist and Chief of Neurosurgery at MGH, a Professor of Neurosurgery at Harvard Medical School, and one of the study’s authors. In the MGH press release he said, “We envision the future integration of tests like this one into the clinical care of our patients with brain tumors. For example, if a patient has a suspected mass on MRI scanning, we can take a blood sample before the surgery and assess the presence of the tumor signature in the blood and then use this signature as a baseline to monitor as the patient later receives treatment, both to gauge response to the treatment and gain early insight into any potential recurrence.” What Carter describes is precision medicine and could open new diagnostic opportunities for anatomic pathology groups and clinical laboratories. (Photo copyright: Massachusetts General Hospital.)

MGH’s Ten-Fold Improvement over Previous ddPCR Assays

A liquid biopsy is the sampling and analysis of non-solid tissue in the body—primarily blood. MGH’s liquid-biopsy method detects cancer by examining fragments of tumor DNA circulating in the bloodstream. Since the technique is mostly non-invasive, tests can be performed more frequently to track tumors and mutations and monitor treatment progression. Prior to this new method, brain tumors had been difficult to detect using liquid biopsies.

“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,” Balaj said in the press release.

However, MGH’s new ddPCR assay has an overall sensitivity rate of 62.5% and a specificity of 90%, which represents a tenfold improvement over prior assays for TERT mutations in the blood.

And when testing the performance of the ddPCR assay in tumor tissue, the MGH researchers discovered their results were the same as results from a previous independently-performed clinical laboratory assessment of TERT mutations within collected tumor specimens. They also found that their assay could detect TERT mutations when looking at blood plasma samples collected at other facilities.

The researchers believe that their test could be performed in most clinical laboratories and can be utilized to follow the course of disease in cancer patients. The MGH researcher’s goal is to expand and adapt the blood test to diagnose, differentiate, and monitor other types of brain tumors in addition to gliomas.

Of course, more research will be needed before MGH’s new assay can become a vital tool in the fight against disease. However, this type of genetic analysis may soon provide pathologists with new techniques to more accurately diagnose and monitor cancers, and to provide healthcare providers with valuable data regarding which therapies would be the most beneficial for individual patients, a key element of precision medicine. 

—JP Schlingman

Related Information:

Breakthrough Blood Test Developed for Brain Tumors

TERT Promoter Mutation Analysis for Blood-based Diagnosis and Monitoring of Gliomas