ATRT-07. CLINICAL APPLICABILITY OF C19MC MIRNA DETECTION IN LIQUID BIOPSIES OF ETMR PATIENTS

Abstract

Abstract Embryonal tumor with multilayered rosettes (ETMR) is a distinct central nervous system tumor entity which is characterized by dysregulation of oncogenic micro RNAs (miRNA). In the majority of cases (approx. 90%), tumors are characterized by amplification of the C19MC locus accompanied by a fusion of this locus to the TTYH1 gene. Beside the very young age of the patients, ETMR is a highly aggressive brain tumor with a dismal clinical outcome. About half of the patients relapse within the first 6 months despite intensive therapy. Based on these facts, a more rapid diagnosis as well as more accurate and faster detection of tumor response or tumor relapse would significantly improve the management of these severely affected young patients. Liquid biopsy has emerged as a highly promising tool to enable minimal invasive detection of molecular parameters to facilitate diagnosis and patient monitoring. Here, we developed a miRNA based liquid biopsy tool and performed a comprehensive profiling of the miRNA landscape in 11 ETMR tumor tissues and matching liquid biopsy samples of patients. The screening of the initial liquid biopsy samples (plasma or serum) taken at diagnosis revealed distinctly enriched miRNA levels. Further, we evaluated the use of the miRNA levels as a longitudinal tumor-monitoring tool. We detected decreasing levels after tumor resection and in long-term survivors and vice versa increasing levels in patients with progressive tumor disease. In conclusion, we developed a reliable and fast method with a turnaround time of only 4 hours between blood draw and analysis of the aberrant expressed miRNA in liquid biopsy samples of ETMR patients correlating with the clinical course of the individual patient.