Experimental blood test can detect several signs of brain cancer to help improve diagnosis and monitoring

BOSTON- Massachusetts General Hospital (MGH) researchers who previously developed a blood test for mutations in a gene linked to gliomas, the most common type of brain tumor in adults, have now applied their technology to detect additional mutations, in this case in the gene that codes for the epidermal growth factor receptor (EGFR).

The breakthrough, which is described in a study published in Clinical cancer researchprovides clinicians with a powerful tool to detect the presence of gliomas, characterize tumors and monitor their condition after treatment.

The team’s test is a form of liquid biopsy that detects bits of tumor cell genetic material, called mRNA, circulating in the blood.

A previous study first reported the technique, a novel highly optimized digital droplet polymerase chain reaction (ddPCR) blood test, to accurately detect and monitor the presence of two gene mutations TERwhich is commonly mutated in glioma tumors.

After adapting their technique to detect mRNA produced from a EGFR gene called EGFRvIII which is often present in particularly aggressive gliomas, the researchers determined the prevalence of EGFRvIII mRNA in glioma tumor tissue from 37 tumor tissue samples, and they tested their blood test in plasma samples from 30 glioma patients with tissue confirmation EGFRvIII10 patients with gliomas without EGFR mutations and 14 healthy controls.

The team reported that the blood test had overall sensitivity (ability to detect the presence of EGFRvIII) of 72.8% and a specificity (ability to detect the absence of EGFRvIII) by 97.7%.

“There is a real need to make the diagnosis of brain tumors less invasive than the current technique of tissue biopsy. This research demonstrates that it is now possible to diagnose a brain tumor via a blood test for one of the most common mutations detected in brain tumors,” says co-lead author Leonora Balaj, PhD, Research Center Investigator on brain tumors at the MGH and researcher. assistant professor of neurosurgery at Harvard Medical School.

The technology could also be used to determine which patients are most likely to benefit from drugs targeting the EGFRvIII protein on cancer cells. “Current studies involving CAR-T immune cells aim to target this surface marker. A blood test for EGFRvIII would help stratify patients who would be eligible for potential clinical trials as well as monitor treatment response using a simple blood test,” says co-lead author Bob S. Carter , MD, PhD, chair of the Department of Neurosurgery at the MGH and William and Elizabeth Sweet Professor of Neurosurgery at Harvard Medical School.

Scientists note that their EGFR and TER the tests will require further studies to assess their performance in larger patient groups; however, the combination of different mutation assays represents a promising strategy to more accurately diagnose gliomas, monitor tumor progression, and assess response to treatment. The technology could also be applied to a range of other types of cancer that carry mutations in these and other genes.

Additional co-authors include Syeda Maheen Batool, Koushik Muralidharan, Tiffany Hsia, Sarah Falotico, Austin S. Gamblin, Yulia B. Rosenfeld, and Sirena K. Khanna.

Funding for the study was provided by the National Institutes of Health and the Rappaport Foundation.

About Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is Harvard Medical School’s first and largest teaching hospital. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and includes more than 9,500 researchers working in more than 30 institutes, centers and departments. In August 2021, Mass General was named #5 in the US News and World Report list of “America’s Best Hospitals”. MGH is a founding member of the Mass General Brigham Health System.

Lillian L. Pena