Summary: Researchers have developed a personalized blood test that may offer a faster, less invasive way to track high-grade glioma progression. By identifying unique DNA junctions from each patient’s tumor, the test can detect tumor DNA in the bloodstream, even before changes appear on MRI scans.
These DNA fragments bypass some limitations of the blood-brain barrier, offering a sensitive early warning for disease advancement. The test detected tumor activity in 93% of cases, showing promise as a clinical tool for tailoring treatments and monitoring outcomes in real time.
Key Facts:
- DNA Junction Focus: Researchers targeted tumor-specific DNA junctions, which are more abundant and easier to detect than other fragments.
- Early Detection: Tumor DNA levels in blood sometimes rose before any visible MRI changes, offering earlier insights.
- High Accuracy: The personalized test detected tumor DNA in 93% of patients with known DNA junctions.
Source: Mayo Clinic
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.
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 lead author George Vasmatzis, Ph.D., 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.”
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.
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 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 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 tumor tracking correlates with glioma progression across a larger group of patients.
About this brain cancer and genetics research news
Author: Sharon Theimer
Source: Mayo Clinic
Contact: Sharon Theimer – Mayo Clinic
Image: The image is credited to Neuroscience News
Original Research: Closed access.
“Personalized Tumor-Specific Amplified DNA Junctions in Peripheral Blood of Patients with High-Grade Gliomas” by George Vasmatzis et al. Clinical Cancer Research
Abstract
Personalized Tumor-Specific Amplified DNA Junctions in Peripheral Blood of Patients with High-Grade Gliomas
Purpose:
Monitoring disease progression in patients with high-grade gliomas (HGG) is challenging due to treatment-related changes in imaging and the requirement for neurosurgical intervention to obtain diagnostic tissue. DNA junctions in HGG often amplify oncogenes, making these DNA fragments potentially more abundant in blood than monoallelic mutations.
In this study, we piloted a cell-free DNA approach for disease detection in the plasma of patients with HGG by leveraging patient-specific DNA junctions associated with oncogene amplifications.
Experimental Design:
Whole-genome sequencing of grade 3 or 4 isocitrate dehydrogenase–mutant or wild-type astrocytomas was utilized to identify amplified junctions. Individualized qPCR assays were developed using patient-specific primers designed for the amplified junction. ctDNA levels containing these junctions were measured in patient plasma samples.
Results:
Unique amplified junctions were evaluated by individualized semi-qPCR assays in presurgical plasma of 18 patients, 15 with tumor-associated focal amplifications and three without tumor-associated focal amplifications. high copy-number junctions were robustly detected in the plasma of 14 of 15 (93.3%) patients with amplified junctions and none of the controls.
Changes in junction abundance correlated with disease trajectory in serial plasma samples from five patients, including increased abundance of amplified junctions preceding radiographic disease progression.
Conclusions:
In patients with grade 3 or 4 astrocytomas who had tumor-associated amplifications, patient-specific amplified junctions were successfully detected in assayed plasma from most patients. Longitudinal analysis of plasma samples correlated with disease trajectory, including cytoreduction and progression.
