Exploring genetic alterations in circulating tumor DNA from cerebrospinal fluid of pediatric medulloblastoma

Medulloblastoma (MB) is the most common type of brain malignancy in children. Molecular profiling has become an important component to select patients for therapeutic approaches, allowing for personalized therapy. In this study, we successfully identified detectable levels of tumor- derived cell-free DNA (cfDNA) in cerebrospinal fluid (CSF) samples of patients with MB. Furthermore, cfDNA from CSF can interrogate for tumor-associated molecular clues. MB-associated alterations from CSF, tumor, and post-chemotherapy plasma were compared by deep sequencing on next-generation sequencing platform. Shared alterations exist between CSF and matched tumor tissues. More alternations were detected in circulating tumor DNA from CSF than those in genomic DNA from primary tumor. It was feasible to detect MB-associated mutations in plasma of patients treated with chemotherapy. Collectively, CSF supernatant can be used to monitor genomic alterations, as a superior technique as long as tumor-derived cfDNA can be isolated from CSF successfully.

Automated summary

In this study, detectable levels of tumor-derived cfDNA were identified in cerebrospinal fluid (CSF) samples from medulloblastoma (MB) patients, indicating the potential of using CSF as a source for monitoring genomic alterations. The study also found more alterations in circulating tumor DNA from CSF compared to genomic DNA from primary tumor, and observed the feasibility of detecting MB-associated mutations in plasma of patients undergoing chemotherapy.