820 New Insights into the Genomic Landscape of Skull Base Meningiomas

Abstract

INTRODUCTION: The management of skull base meningiomas is challenging due to their complexity and proximity to crucial nearby structures. The identification of oncogenic mutations has provided further insights into the tumorigenesis of meningioma and the possibility of targeted therapy. METHODS: Tissue samples were collected from 71 patients diagnosed with meningioma from 2008 to 2016. Tissues were treated and archived as formalin-fixed paraffin-embedded (FFPE). Samples were subjected to targeted sequencing using a customized gene panel. RESULTS: The study cohort comprised 71 patients with histologically proven meningioma (grades I, II, and III) .The median patient age was 54.8 years (range 27-96 years). Most of the patients were female (51/71, 72.82%), while 19/71 (27.14%) were male. 56/71 patients had grade I (80.0%), 13/71 (18.57%) had grade II and 1/71 (1.428%) had grade III tumors. A total of 51/71 of the tumors were found in the skull base (72.82%). 22/71 (31.42%) of the tumors were meningothelial, 6/71 (8.57%) were atypical, 6/71 (8.57%) were transitional, 3/71 (4.28) were secretory, and 2/71 (2.86%) were chordoid. We detected an average of 1.56 ± 1.07 genomic alterations (GAs) per patient. the most common mutations were in NF2 (52/71), PIK3CA (22/71), FGFR3 (13/71), SMO (11/71) and AKT1 (10/71), with Tertp (1/71) mutations being the least frequent. The NF2-positive tumors were predominantly of grade I 43/52 (82.69%) with lower rates of recurrence (7/52, 13.41%) in tumors harboring NF2 mutations compared to tumor harboring non-NF2 mutations (8/18, 44.44%). Single FGFR3 mutations reported in three patients, all had WHO grade I tumors, with no recurrence in our cohort. CONCLUSIONS: This cohort focusing skull base meningiomas, highlights a range of mutations outside the known cancer driver NF2 that may be linked to meningioma prognosis. Among our findings were the identification of a rare TERTp mutation and the first report of FGFR3 mutations that may represent biomarkers for the identification of skull base meningioma patients with a favorable prognosis. Taken together, these findings highlight how genetic profiling can guide optimal treatment strategies, prognostic prediction, and patient management for skull meningioma.