BIOM-54. ENRICHMENT OF BRAIN TUMOR-DERIVED CTDNAS AND MICRORNAS IN BLOOD CIRCULATION IN PATIENTS USING SONOBIOPSY

Abstract INTRODUCTION Blood-based liquid biopsy offers a non-invasive alternative to traditional surgical biopsies for brain cancer diagnosis. However, the blood-brain barrier (BBB) often restricts the transfer of brain tumor-derived molecular biomarkers into the blood, complicating sensitive molecular diagnosis. Sonobiopsy utilizes focused ultrasound (FUS) and microbubbles to temporarily open the BBB, facilitating the release of brain tumor-specific biomarkers into the blood. This sonobiopsy clinical study aims to evaluate the efficacy of sonobiopsy in enriching ciruclating tumor DNAs (ctDNAs) and microRNAs for sensitive molecular characterization of brain tumors. METHODS Sonobiopsy procedures were performed pre-resection using a customized FUS device integrated with a clinical neuronavigation system. Blood samples were collected pre- and post-FUS intervention for analyzing the enrichment of circulating tumor biomarkers with sonobiopsy. Personalized Cancer Monitoring assays (Invitae) were utilized to analyze plasma ctDNAs in five glioma patients. Small RNA sequencing was employed to profile plasma microRNAs in eleven glioma patients. RESULTS Firstly, sonobiopsy enhanced the detection of tumor-derived DNA biomarkers in plasma. This enhancement resulted in a maximum increase of 1.6-fold in mono-nucleosomal cfDNA fragments, a 1.9-fold increase in patient-specific ctDNAs, and a substantial 5.6-fold increase in TERT mutation. Sonobiopsy also improved the detection of tumor-derived microRNAs in plasma: low expressing microRNAs in 10 patients and medium expressing microRNAs in 8 patients, but not high expressing microRNAs. Following FUS sonication, mean plasma levels of low expressing microRNAs increased 3.5-fold, while those of medium expressing microRNAs increased 1.2-fold. Notably, microRNAs such as miR-122-5p, miR-1271-5p, miR-377-5p, miR-1275, and miR-18a-3p were correlated with sonobiopsy enrichment and are involved in the regulation of glial cell development and neuron organization. CONCLUSIONS These findings underscore the potential of sonobiopsy for non-invasive molecular characterization of brain tumors and support further investigation into its clinical applications.