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 personalised blood test tailored to each patient's tumour 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 tumour 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 tumour changes over time and adjust treatment as needed.
The findings focus on tumour 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 tumour.
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 defence that prevents many substances from leaving the brain.
To overcome this limitation, researchers focused on DNA junctions, a type of tumour-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 tumour progression.
Unlike normal DNA, which follows a structured sequence, these DNA junctions form when the tumour'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 lead author George Vasmatzis, Ph.D., co-director of the Biomarker Discovery Programme at Mayo Clinic's Centre for Individualised Medicine and Mayo Clinic Comprehensive Cancer Centre.
"It offers new possibilities for patient-specific monitoring and targeted interventions."
In the study, researchers analysed samples from patients with high-grade gliomas.
They used whole genome sequencing to map each tumour's unique genetic blueprint and pinpointed patient-specific DNA junctions.
Researchers then developed personalised blood tests to search for these genetic markers in plasma.
The test detected tumour DNA in approximately 93% of the cases where these DNA junctions were present.
In some patients, tumour DNA levels in the blood rose before MRI scans showed any changes — offering a potential early signal for disease progression.
Connecting cutting-edge research and clinical practice, Dr. Vasmatzis and Terry Burns, M.D., Ph.D., a neurosurgeon at Mayo Clinic in Rochester, Minnesota, collaborated on the research.
"By tracking each tumour's distinct molecular signature, we're aiming to shift from a reactive approach to one that's far more proactive," says Dr. Burns, a study co-author.
"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 tumour tracking correlates with glioma progression across a larger group of patients.
Review the study for a complete list of authors, disclosures and funding.
Source: Mayo Clinic
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