Despite excellent progress being made into diagnosing and treating brain cancers, they are still the leading cause of childhood death. To improve outcomes, early detection and monitoring are essential, with liquid biopsies recently emerging as a promising approach to detect brain tumours through the screening of circulating tumour DNA.
A recent study tested the limits of liquid biopsies when used to detect and monitor primary and metastatic childhood brain cancers, with the research demonstrating the feasibility of using personalised liquid biopsies during the surveillance of tumours.
Why funding research is so important
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The importance of the study
Tumour resections and MRI scans are currently the primary methods for treating, diagnosing, and monitoring tumours post-surgery, however the loss of tissue samples is a challenge when classifying the tumours. In addition, malignant cells often evolve, and single biopsies does not represent the tumour fully, especially over a period of time.
In previous studies, the majority of paediatric liquid biopsy samples did not contain sufficient somatic mutations, which lead to low detection rates. In addition, previous studies showed high degrees of fluctuations, and so far, research has not met clinical requirements. Although current tumour screenings are highly specific, the lack of sensitivity reduces confidence and there is a need to improve diagnostic and monitoring methods.
The aim of this study was to characterise the DNA profiles of 12 patients with medulloblastomas, ependymomas, central nervous system neuroblastomas, and embryonal tumours with multi-layered rosettes, in cases where the genome type was relatively stable. By improving on the shortcomings of previous liquid biopsy techniques through a highly personalised approach, the researchers were able to identify somatic mutations within tumour tissue to validate the use of liquid biomarkers.
What did the study find?
12 patient samples were obtained from children with primary brain malignancies, with freshly resected brain tumour tissue collected as part of standard clinical procedures. The cohort of patients included 7 medulloblastomas, 3 ependymomas, 1 ETMR and 1 CNS neuroblastoma patient, who had all received chemotherapy and radiotherapy.
The study involved the collection of 79 liquid biopsies, with the majority of samples taken 1 week after surgery. The researchers extracted the ctDNA and measured its integrity using Bioanalyser microchips, with the electropherograms showing distinct peaks. In 74 out of the 79 samples, there were no genomic DNA fragments found. The team also used molecular profiling to search for mutations within the common driver genes, with the findings revealing that most genes were not mutated.
The findings of this patient-specific approach shows that a highly personalised liquid biopsy method can be used to provide sensitive and efficient detection and surveillance of various brain cancer tumours in children. During the various experiments over the course of the study, the biopsies were able to text as little as 0.17 ng in 1 ml of CSF, representing a higher degree of accuracy than previous studies.