So researchers from the Cancer Research UK Cambridge Institute have developed two simple tests that can detect the presence of glioma, a type of brain tumour, in patient's urine or blood plasma.
Principle of these tests:
Blood tests for detecting different cancer types are based on finding mutated DNA, shed by tumour cells when they die, known as cell-free DNA (cfDNA). Detecting brain tumour cfDNA in the blood has historically been difficult because of the blood-brain-barrier, which separates blood from the cerebrospinal fluid (CSF) that surrounds the brain and spinal cord, preventing the passage of cells and other particles, such as cfDNA. Researchers have previously looked at detecting cfDNA in CSF, but the spinal taps needed to obtain it can be dangerous for people with brain tumours so are not appropriate for patient monitoring.
cfDNA with similar mutations to the original tumour can be found in blood and other bodily fluids such as urine in very low levels, but the challenge has been developing a test sensitive enough to detect these specific mutations.
The researchers at, Cancer Research UK Cambridge Institute have developed two diagnostic tests in parallel to overcome the challenge of detecting brain tumour cfDNA.
First test: finding DNA errors
The first test works for patients who have previously glioma that is removed and biopsied. The team designed a tumour-guided sequencing test that was able to look for the mutations found in the tumour tissue within the cfDNA in the patient’s urine, CSF, and blood plasma.
- Study on Patients - Total eight patients who had suspected brain tumours based on MRIs were included in this part of the study. Samples were taken at their initial brain tumour biopsies, alongside CSF, blood and urine samples. By knowing where in the DNA strand to look, the researchers found that it was possible to find mutations even in the tiny amounts of cfDNA found in the blood plasma and urine.
- Results of first test - The test was able to detect cfDNA in 7 out of 8 CSF samples, 10 out of the 12 plasma blood samples and 10 out of the 16 urine samples.
Second test: Using machine learning algorithms
The second test works for patterns that could also indicate the presence of a tumour, without having to identify the mutations.
- Study on patients - 35 samples were analysed from glioma patients, 27 people with non-malignant brain disorders, and 26 healthy people. They used whole genome sequencing, where all the cfDNA of the tumour is analysed, not just the mutations.
- Results of second test - They found in the blood plasma and urine samples that fragments of cfDNA, which came from patients with brain tumours were different sizes than those from patients with no tumours in CSF. They then fed this data into a machine learning algorithm which was able to successfully differentiate between the urine samples of people with and without glioma.
Benifits of these new tests:
The researchers suggest that their tests could be used between MRI scans, and could ultimately be able to detect a returning brain tumour earlier. The next stage of this research will see the team comparing both tests against MRI scans in a trial with patients with brain tumours who are in remission to see if it can detect if their tumours are coming back at the same time or earlier than the MRI. If the tests prove that they can detect brain tumours earlier than an MRI, then the researchers will look at how they can adapt the tests so they could be offered in the clinic, which could be within the next ten years.
“We believe the tests we’ve developed could in the future be able to detect a returning glioma earlier and improve patient outcomes,” said Mair. “Talking to my patients, I know the three-month scan becomes a focal point for worry. If we could offer a regular blood or urine test, not only will you be picking up recurrence earlier, you can also be doing something positive for the patient’s mental health.”
Michelle Mitchell, Chief Executive of Cancer Research UK said, “While this is early research, it’s opened up the possibility that within the next decade we could be able to detect the presence of a brain tumour with a simple urine or blood test. Liquid biopsies are a huge area of research interest right now because of the opportunities they create for improved patient care and early diagnosis. It’s great to see Cancer Research UK researchers making strides in this important field.”
Sue Humphreys, from Wallsall, a brain tumour patient, said: "If these tests are found to be as accurate as the standard MRI for monitoring brain tumours, it could be life changing.
If patients can be given a regular and simple test by their GP, it may help not only detect a returning brain tumour in its earliest stages, it can also provide the quick reassurance that nothing is going on which is the main problem we all suffer from, the dreaded Scanxiety.
The problem with three-monthly scans is that these procedures can get disrupted by other things going on, such as what we have seen with the Covid pandemic. As a patient, this causes worry as there is a risk that things may be missed, or delayed, and early intervention is the key to any successful treatment.”
- Florent Mouliere et al. ‘Fragmentation patterns and personalized sequencing of cell-free DNA in urine and plasma of glioma patients.’ EMBO Molecular Medicine (2021). DOI: 10.15252/emmm.202012881
- Adapted from a Cancer Research UK press release.
