Abstract
The molecular characterisation of medulloblastoma, the most common paediatric brain tumour, is crucial for the correct management and treatment of this heterogenous disease. However, insufficient tissue sample, the presence of tumour heterogeneity, or disseminated disease can challenge its diagnosis and monitoring. Here, we report that the cerebrospinal fluid (CSF) circulating tumour DNA (ctDNA) recapitulates the genomic alterations of the tumour and facilitates subgrouping and risk stratification, providing valuable information about diagnosis and prognosis. CSF ctDNA also characterises the intra-tumour genomic heterogeneity identifying small subclones. ctDNA is abundant in the CSF but barely present in plasma and longitudinal analysis of CSF ctDNA allows the study of minimal residual disease, genomic evolution and the characterisation of tumours at recurrence. Ultimately, CSF ctDNA analysis could facilitate the clinical management of medulloblastoma patients and help the design of tailored therapeutic strategies, increasing treatment efficacy while reducing excessive treatment to prevent long-term secondary effects.
Highlights
The molecular characterisation of medulloblastoma, the most common paediatric brain tumour, is crucial for the correct management and treatment of this heterogenous disease
In order to assess whether the analysis of cerebrospinal fluid (CSF) circulating tumour DNA (ctDNA) could be a tool for the diagnosis and monitoring of MB patients, tumour, blood and CSF samples were collected from 13 patients (Fig. 1a)
We found that 98.9% (88/89) of the mutations detected in the primary tumour sample with variant allele frequency (VAF) > 5% could be detected in the matching CSF ctDNA
Summary
The molecular characterisation of medulloblastoma, the most common paediatric brain tumour, is crucial for the correct management and treatment of this heterogenous disease. We report that the cerebrospinal fluid (CSF) circulating tumour DNA (ctDNA) recapitulates the genomic alterations of the tumour and facilitates subgrouping and risk stratification, providing valuable information about diagnosis and prognosis. A relatively noninvasive method to characterise primary and relapsed tumours and monitor the evolution of the disease is required to assist the clinical management of MB patients In this regard, liquid biopsies and in particular cell-free circulating tumour DNA (ctDNA) have opened an avenue of research[16]. The analysis of ctDNA in the CSF better reflects the brain tumour genomic alterations than in plasma, it can be used as a molecular diagnostic tool and the dynamic changes during patient monitoring recapitulate the disease course[18,21,22,23,24,25]
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