BIOM-62. CIRCULATING TUMOR CELLS IN MEDULLOBLASTOMA: A NOVEL PERIPHERAL BIOMARKER FOR CNS DISEASE

Abstract BACKGROUND Medulloblastoma is an embryonal tumor of the cerebellum and the most common pediatric malignancy of the central nervous system (CNS). Diagnosis, staging, and disease monitoring require invasive neurosurgical biopsy or MRI. No blood or cerebrospinal fluid (CSF) biomarkers exist. We demonstrate the presence of circulating tumor cell clusters (CTCCs) in patients with medulloblastoma and use a transcriptomic approach to describe their gene expression. Design/Method: We enrolled 34 total patients in a longitudinal study: 24 with medulloblastoma and 10 without malignancy. CTCCs are captured from unprocessed whole blood using a physics-based label-free approach to CTCC isolation. RNA sequencing was performed on 21 samples at time of diagnostic resection from 6 patients with medulloblastoma. Sequencing reads were assessed for quality control, trimmed, and aligned to the human genome. Differential gene expression (DGE) was performed against whole blood from healthy controls. Reactome pathway database of curated, peer-reviewed gene sets are used for gene set enrichment analysis (GSEA). RESULTS The presence of peripherally CTCC patients with medulloblastoma is not previously known and was detected in all patients with medulloblastoma whereas none were observed from patients with non-malignant hematological conditions. RNA-sequencing demonstrate separation on principal component analysis and gene-expression heatmap against whole blood healthy control. DGE shows upregulation of genes indicating stem-like state. GSEA show enrichment of medulloblastoma molecular pathways and gene sets defining integrin, extracellular matrix remodeling, and cell adhesion pathways. Transient elevation of peripheral CTCC followed by return to baseline levels was associated with durable disease response to therapy, whereas persistence or elevation of CTCC in CSF correlated with disease recurrence. CONCLUSION The universal and specific finding of peripherally captured CTCC arising from parent tumor in the CNS within our patient cohort suggests a utility as a tumor biomarker. Future sequencing is planned comparing CTCC transcriptome against parent tumor.