Mayo Clinic researchers have identified a potential new way to monitor the progression of high-grade gliomas, one of the most aggressive types of brain cancer. Their feasibility study suggests that a personalized blood test tailored to each patient's tumor DNA could provide a faster and less invasive way to determine if the cancer is advancing. 

Currently, clinicians rely on scans and surgical biopsies to monitor gliomas, but both methods have limitations. For example, scans often cannot distinguish tumor growth from treatment effects such as inflammation. Biopsies require invasive procedures, making them impractical for routine monitoring. 

This new approach, published in Clinical Cancer Research, may provide clinicians with another tool to monitor tumor changes over time and adjust treatment as needed. 

Tracking DNA fragments of gliomas

The findings focus on tumor DNA fragments circulating in the blood. As gliomas grow, some glioma cells die, shedding pieces of their DNA into the bloodstream and leaving behind genetic markers that are unique to the tumor. 

However, gliomas release fewer DNA fragments into the blood compared to many other cancers. This is because of the blood-brain barrier, a natural brain defense that prevents many substances from leaving the brain.  

To overcome this limitation, researchers focused on DNA junctions, a type of tumor-specific DNA fragment that is present in higher quantities. By targeting these markers, researchers achieved greater sensitivity, enabling them to detect even the smallest signs of tumor progression. 

Unlike normal DNA, which follows a structured sequence, these DNA junctions form when the tumor's genetic material breaks and rearranges. The study found that these amplified DNA junctions, due to their higher numbers, may provide a clearer picture of disease progression. 

"This research builds on years of studying genetic rearrangements and gives us a deeper understanding of the molecular mechanisms driving gliomas," says George Vasmatzis, Ph.D., a lead author of the study and co-director of the Biomarker Discovery Program at Mayo Clinic's Center for Individualized Medicine and Mayo Clinic Comprehensive Cancer Center. "It offers new possibilities for patient-specific monitoring and targeted interventions." 

Detecting tumor DNA

In the study, researchers analyzed samples from patients with high-grade gliomas. They used whole genome sequencing to map each tumor's unique genetic blueprint and pinpointed patient-specific DNA junctions. Researchers then developed personalized blood tests to search for these genetic markers in plasma. 

The test detected tumor DNA in approximately 93% of the cases where these DNA junctions were present. In some patients, tumor DNA levels in the blood rose before MRI scans showed any changes — offering a potential early signal for disease progression.

Dr. Vasmatzis collaborated with Mayo Clinic neurosurgeon Terry Burns, M.D., Ph.D., bridging the gap between cutting-edge research and clinical practice. 

"By tracking each tumor's distinct molecular signature, we're aiming to shift from a reactive approach to one that's far more proactive," says Dr. Burns, a co-author of the study. "This research could lay the groundwork for tools that help clinicians make the most informed treatment decisions as early as possible." 

Future studies will evaluate how well blood-based tumor tracking correlates with glioma progression across a larger group of patients. 

Review the study for a complete list of authors, disclosures and funding.   

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