Diagnostics of Glioma Tumor by Non-Invasive Liquid Biopsy using Circulating Tumor DNA in Plasma

Dr. Frenkel-Morgenstern, the Azrieli Faculty of Medicine, and Prof. Tali Siegal, from the Neuro-Oncology Department, Rabin Medical Centre, have been collaborating for the last three years in developing a liquid biopsy platform for glioblastoma patients using circulating cell-free DNA (cfDNA), particularly circulating tumor DNA (ctDNA) in blood plasma of patients. Currently, glioblastoma, which is the most dangerous type of brain tumour, is resistant to both radiotherapy and chemotherapy regimens with the average survival of 15 months. The collaborative project has already collected samples from 20 patients, including samples obtained from Midgam (The Israeli National Tissue Bank); and in collaboration with Prof. Rainer Grass, Neurosurgical Research, University Clinics Munich, Germany, and Prof. Michael Synowitz, Department of Neurosurgery, UKSH, Campus Kiel, Germany. The liquid biopsy platform, which has been developed by the PhD student, Vikrant Palande and by Dr. Dorith Raviv-Shay, the lab manager at the Frenkel-Morgenstern`s lab, has been able to distinguish sensitively between cancer patients and normal controls (95% specificity, 80% sensitivity). Moreover, unique pathogenic mutations identified in ctDNA corresponded to the mutations appearing in the tumour biopsies (80% sensitivity). Interestingly, one "suspected" patient who was tested by three independent liquid biopsy tests showed unexpectedly low amounts of ctDNA in their plasma. From our experience, we suggested that this patient might not have glioblastoma. After three months, this patient was finally confirmed as non-cancerous, by means of multiple MRI images, surgery and clinical workup. Today, this patient`s condition has improved and he is considered healthy. This case and others suggest high potential of the sensitivity of our liquid biopsy platform for brain tumors.