PATH-35. AKT1(E17K) MUTATIONS ARE FREQUENT GENOMIC EVENTS IN CERVICAL SPINAL MENINGIOMAS

Abstract

Abstract INTRODUCTION Spinal meningiomas represent about one-third of all spine tumors. To date, little is known about the molecular profile of spinal meningiomas and their clinical impact. In this study, we correlate clinical parameters with targeted sequencing findings in a well-characterized cohort of 42 patients with spinal meningiomas. METHODS Samples from 42 spinal meningiomas (31 females and 11 males) were collected. Targeted sequencing for AKT1 E17K hot spot mutations was performed. Furthermore, clinical and imaging data were collected and correlated with the AKT1 mutation status. RESULTS Gross total resection (Simpson grade I /II) was achieved in all patients. The mean follow-up period was 60 months (6 –288 months). None of the patients demonstrated a tumor recurrence. AKT1E17K mutations were detected in 8 patients (19%), in five male and three female patients (p= 0.019). Although the majority of resected meningiomas (n= 28, 66.6%) were located in the thoracic spine, meningiomas originating in the cervical spine harbored significantly more AKT1 E17K mutations (6 out of 14, p= 0.010). Notably, all AKT1 mutated meningiomas arose ventrally or ventrolaterally to the spinal cord. The histologic examination revealed a WHO Grade 1 in 36 meningiomas (85.7%): 21 meningothelial, 8 psammomatous, 5 transitional, 2 fibrous. The remaining six meningiomas were classified as atypical WHO grade 2. Remarkably, AKT1 E17K mutations were significantly related to a meningothelial subtype (p= 0.044). CONCLUSIONS Our molecular study demonstrates that AKT1 E17K mutations are a frequent genomic event in spinal meningiomas. The majority of AKT1 mutated meningiomas occurred in male patients, originate in the cervical spine, and exhibit meningothelial histology.