Detection and treatment of brain cancer have historically presented a challenge for researchers and clinicians. However, with new techniques such as liquid biopsy and advanced sequencing methods, identifying tumors in the brain could become considerably easier. Now investigators from the Cambridge Institute at Cancer Research UK (CRUK) have made considerable progress in the development of fluid biopsies for brain tumors by detecting tumor DNA in the fluid around the brain and the spine. Biological biopsies are fluid samples from patients, for example from blood or urine, which provide a less invasive way to monitor disease compared to tumor biopsies. A less intrusive test could be extremely beneficial for brain tumors where the collection of samples can be difficult and risky for patients.
The findings of the new study were published today in EMBO Molecular Medicine through an article titled "Detection of cell-free DNA fragmentation and changes in the number of children in cerebrospinal fluid from patients with glioma."
Liquid biopsies show a great promise for a number of cancers, but tests for brain tumors have lagged behind because of low levels of tumor DNA found in body fluids, particularly blood, explains study investigator in collaboration Florent Mouliere, Ph.D., who led the work as a scientist at Cancer Research UK Cambridge Institute. Our work shows that a cheap, easily accessible technique can be used to analyze tumor DNA in the cerebrospinal fluid. In the future, we thought this technique could be used to identify patients who could benefit from additional tests that could help monitor their disease, opening more tailored treatment approaches.
In the current study, scientists at the Cancer Research UK Cambridge Institute have analyzed the cerebrospinal fluid (CSF) – which spins the brain and spinal cord – in 13 patients with a type of brain tumor called glioma. Amazingly, they were able to detect tumor DNA in five (39%) of the patients in the study.
Subsequently, the researchers used a cheap and widely available technique called superficial sequencing of the genome to detect brain tumor DNA – the CRUK team looked for large genetic changes such as genes that are duplicated or lost. The researchers were able to identify tumor DNA in CSF by analyzing the size of DNA fragments that are shorter than those in healthy cells. This provides another way to detect brain tumor DNA, potentially increasing the detection rate.
Interestingly, in a patient, multiple tissue samples from the brain tumor were compared to their CSF. Genetic changes largely fit, but CSF contained changes that were missed in some tissue samples, suggesting that CSF samples might reflect the repertoire of genetic changes found in brain tumors.
The survival of brain tumors remains low and there is an urgent need for research to better identify management strategies for these complex diseases. This study sets out the important foundations that make it possible for liquid biopsies for this difficult disease to be treated a step closer, "concludes Chares Swanton, Ph.D., Cancer Research UK's Clinician. Researchers will now need to extend this activity to a larger number of patients and find out if this approach could have applications in the clinic, such as indicating whether a patient's treatment is working.