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Meningiomas are mostly benign CNS tumors, however a subset of these tumors may become atypical or malignant. The standard of care to monitor patients after diagnosis requires serial MRI assessments, which have limited value in distinguishing malignant tumors from benign disease. Therefore the discovery of non-invasive methodologies that reflect meningioma tumor burden and its dynamic evolution in real-time is highly desirable. Liquid biopsy (LB) could be used to fine-tune surveillance and treatment with minimal risk to patients. Evidence of circulating tumor cells and cell-free (cf) tumor DNA in the blood has been shown in several tumor types, however limited progress has been made for brain tumors with known biomarkers; possibly due to the unlikelihood of capturing point mutations in circulating DNA fragments. On the other hand, DNA methylation signatures are maintained even in small DNA fragments, which suggests that DNA methylation is an attractive marker to be studied in liquid biopsy of brain cancers. In order to identify DNA methylation-based biomarkers using archival serum and tissue specimens, we analyzed the epigenome (Illumina Human EPIC array) of patients with primary (n=10) and recurrent (n=4) meningiomas and epileptic patients (n=5) as control. cfDNA fragment size distribution revealed peaks with 150~200bp on average. We identified 482 CpGs (p-value&lt; 0.001) differentially methylated between primary meningiomas and controls, which 294 (61%) show a DNA methylation profile similar to the matched tumor tissue. Overall, we observed that recurrent samples are hypermethylated (56%) compared to primary. From this pilot data, we were able to investigate the LB methylome of meningioma patients and identify potential markers to detect tumor cells in the serum of these patients, which could eventually allow clinicians to monitor impending disease progression and recurrence.

GENE-61. METHYLATION-BASED LIQUID BIOPSY OF MENINGIOMA PRIMARY AND RECURRENT SAMPLES