DNA methylation profiling from cerebrospinal fluid as a diagnostic tool for pineoblastoma

Area of Science:

• Neuro-oncology
• Molecular Diagnostics
• Pediatric Oncology

Background:

• Pineoblastoma is a rare, aggressive pediatric central nervous system (CNS) tumor.
• Accurate diagnosis is difficult due to histological overlap and limited molecular data.
• DNA methylation profiling and cell-free DNA (cfDNA) analysis in CSF are emerging diagnostic tools.

Purpose of the Study:

• To report a challenging case of pineoblastoma diagnosis in a pediatric patient.
• To evaluate the utility of CSF-derived DNA methylation profiling for tumor classification.
• To demonstrate the potential of liquid biopsy in pediatric CNS tumor diagnostics.

Main Methods:

• Analysis of DNA methylation profiling on a low amount of CSF-derived DNA.
• Histopathological re-evaluation of formalin-fixed, paraffin-embedded tissue was not feasible.
• Subsequent tissue-based DNA methylation analysis of a secondary lesion for confirmation.

Main Results:

• CSF-derived DNA methylation profiling accurately classified the tumor as pineoblastoma, subtype miRNA processing altered 1, subclass A.
• The diagnosis enabled timely patient management.
• Epigenetic signature from CSF DNA concordantly matched the secondary lesion's tissue-based DNA methylation profile.

Conclusions:

• CSF-based DNA methylation profiling is a promising, minimally invasive tool for diagnosing pediatric CNS tumors.
• The concordance between CSF and tissue profiling supports integrating liquid biopsy into diagnostic workflows.
• Further studies are needed to validate this approach for other CNS malignancies.