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Scientists can detect brain tumours using a simple urine or blood plasma test

A Schematic of ctDNA detection in matched CSF, plasma, and urine samples from glioma patients using INVAR (Integration of VAriants Reads). The sequence depth shown is the average of the entire analyzed sample. S1 through S4 represent tumor subparts. B The number of DNA mutations in tumor tissue that have passed the INVAR filter of 8 patients. C Estimates of plasma (10/12 detection), CSF (7/8 detection), and urine samples (10/16 detection) collected from 7 and 1 patients (GB12) of primary oligodendroglioma ctDNA fraction) With undifferentiated oligodendroglioma. The ctDNA fraction is represented as IMAF (Integrated Mutant Allele Fraction). Detected cases are indicated by black circles, and undetected cases are indicated by white circles. ND: Not detected. D Estimated tumor DNA DNA fractions (IMAF) in CSF, plasma, and urine, depending on the number of mutant reads detected in each sample included and the number of beneficial reads to support the observation. Detected cases are indicated by black circles, and undetected cases are indicated by white circles. ND: Not detected. E Estimated tumor DNA fractions (IMAF) in CSF, plasma, and urine of matching samples collected preoperatively at baseline. Detected cases are indicated by black circles, and undetected cases are indicated by white circles. ND: Not detected. F IMAF of patients’ CSF, plasma, and urine using samples collected at 6-month follow-up (n = 3). A matching MRI scan is added for annotation. Credit: DOI: 10.15252 / emmm.202012881 “width =” 800 “height =” 530 “/>

Detection of ctDNA in CSF, plasma, and urine of glioma patients using patient-specific sequence panels and INVAR analysis. NS Schematic of ctDNA detection in matched CSF, plasma, and urine samples from glioma patients using INVAR (Integration of VAriants Reads). The sequence depth shown is the average of the entire analyzed sample. S1 through S4 represent tumor subparts. NS The number of tumor tissue DNA mutations that pass through the INVAR filter of the 8 patients included. NS Plasma (10/12 detection), CSF (7/8 detection), and urine samples collected from 7 patients with primary glioblastoma and 1 patient with undifferentiated oligodendroglioma (GB12) Estimated ctDNA fraction (detected on 10/16). The ctDNA fraction is represented as IMAF (Integrated Mutant Allele Fraction). Detected cases are indicated by black circles, and undetected cases are indicated by white circles. ND: Not detected. NS Estimated tumor DNA DNA fractions (IMAF) in CSF, plasma, and urine, depending on the number of mutant reads detected in each sample included and the number of beneficial reads supporting the observations. Detected cases are indicated by black circles, and undetected cases are indicated by white circles. ND: Not detected. E Estimated tumor DNA fractions (IMAF) in CSF, plasma, and urine of matching samples collected preoperatively at baseline. Detected cases are indicated by black circles, and undetected cases are indicated by white circles. ND: Not detected. NS IMAF of patients’ CSF, plasma, and urine using samples collected at 6-month follow-up (n = 3). A matching MRI scan is added for annotation. Credit: DOI: 10.15252 / emmm.202012881

Researchers at Cancer Research UK Cambridge Institute have developed two tests that can detect the presence of glioma, a type of brain tumor in a patient’s urine or plasma.

team is, test To detect glioma using urine It is the first time in the world.

Although the study is published in EMBO molecular medicineAre in the early stages and only a small number of patients have been analyzed, the team states that their results are promising.

Researchers suggest that in the future, GPs may be able to use these tests to monitor high-risk patients. brain tumor. This can be more convenient than the standard method of doing an MRI every three months.

Resection of a brain tumor increases the chance of recurrence, so an MRI scan is done every three months followed by a biopsy.

Blood tests to detect different types of cancer are the main focus of research by teams around the world, some of which are used in clinics. These tests are primarily based on the discovery of mutant DNA, known as cell-free DNA (cfDNA), that is released when tumor cells die.

However, detection of brain tumor cfDNA blood The blood-brain barrier has historically been difficult because it separates blood from the cerebrospinal fluid (CSF) that surrounds the brain and spinal cord, blocking the passage of cells and other particles such as cfDNA.

Researchers have previously considered detecting cfDNA in CSF, but the spinal puncture required to obtain it can be dangerous for people with brain tumors and is not suitable for patient monitoring. Hmm.

Scientists know that cfDNA with mutations similar to the original tumor is found at very low levels in other body fluids such as blood and urine, but enough to detect these specific mutations. The challenge is to develop a sensitive test.

Developed by researchers led by Dr. Florent Mouliere, based at Cancer Research UK Cambridge Institute and Rosenfeld Lab in Amsterdam UMC, and Dr. Richard Mair, based at Cancer Research UK Cambridge Institute and University of Cambridge. Two parallel approaches to overcome the challenge of detecting brain tumor cfDNA.

The first approach is useful for patients who have previously had a glioma removed and biopsied.The team includes the patient’s urine, CSF, and plasma..

A total of eight patients with suspected brain tumors based on MRI were included in this part of the study. Samples were taken on the first brain tumor biopsy, along with CSF, blood, and urine samples.

By knowing where to look in the DNA strand, researchers have found that mutations can be found in even small amounts of cfDNA in plasma and urine.

This test was able to detect cfDNA in 7 of 8 CSF samples, 10 of 12 plasma blood samples, and 10 of 16 urine samples.

In the second approach, researchers searched for other patterns of cfDNA that could indicate the presence of tumors without identifying mutations.

They analyzed 35 samples from glioma patients, 27 with non-malignant brain disorders, and 26 healthy people. They used a whole-genome sequence in which all cfDNA of the tumor was analyzed, not just mutations.

They found in plasma and urine samples that fragments of cfDNA from patients with brain tumors were of a different size than fragments of patients without tumors in the CSF. We then entered this data into a machine learning algorithm to successfully distinguish between urine samples in people with and without glioma.

According to researchers, machine learning tests are cheap and easy and do not require tissue biopsy from the tumor, but they are less sensitive and less specific than the first tumor-guided sequencing approach.

MRI is neither invasive nor expensive, but you have to go to the hospital and the 3-month gap between checks can cause regular anxiety for the patient.

Researchers suggest that their tests can be used between MRI scans and may eventually detect recurrent brain tumors early.

In the next phase of this study, can the team compare both tests to MRI scans to detect whether the tumor recurs at the same time as or earlier than MRI in patients with brain tumors in remission? Please check. If the test proves that brain tumors can be detected faster than MRI, researchers will consider how the test can be adapted for delivery in the clinic within the next 10 years.

“We believe that the tests we have developed can detect recurrent gliomas early and improve patient outcomes in the future,” says Mair. “When I talk to my patients, I know that a three-month scan is the focus of concern. If you can provide regular blood or urine tests, not only can you detect recurrence early, but what? You can also do positive things. The patient’s mental health. “

Michelle Mitchell, Chief Executive Officer of Cancer Research UK, said: Blood test.. Liquid biopsy is currently a major area of ​​research interest because it improves patient care and creates opportunities for early diagnosis. It’s great to see researchers at Cancer Research UK making progress in this important area. “

Sue Humphreys of Walsall, a brain tumor patient, said: “If these tests prove to be as accurate as standard MRIs for monitoring brain tumors, they can be life-changing.

If patients can undergo regular and brief examinations by the GP, it not only helps detect recurrent brain tumors in the early stages, but nothing is happening, which is the main problem we all suffer from. A terrifying Scanxiety that can also provide a quick sense of security.

The problem with scanning every three months is that these steps can be interrupted due to other things happening, such as those seen in the COVID pandemic. As a patient, this raises concerns because there is a risk that things will be overlooked or delayed, and early intervention is the key to any successful treatment. ”


A breakthrough blood test developed for brain tumors


For more information:
Florent Mouliere et al, Fragmentation Patterns and Individual Sequencing of Cell-Free DNA in Urine and Plasma in Patients with Glioma, EMBO molecular medicine (2021). DOI: 10.15252 / emmm.202012881

Quote: Scientists, a simple urine or plasma test taken on July 26, 2021 from https: //medicalxpress.com/news/2021-07-scientists-brain-tumours-simple-urine.html (2021) July 26) can be used to detect brain tumors

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