PATH-51. GENETIC CHARACTERIZATION AND MUTATIONAL PROFILING OF FORAMEN MAGNUM MENINGIOMAS: A MULTI-INSTITUTIONAL STUDY

Abstract

Abstract OBJECTIVE Foramen magnum (FM) meningiomas pose significant surgical challenges and have high morbidity and mortality rates. This study aims to investigate the distribution of clinically actionable mutations in FM meningiomas and identify clinical characteristics associated with specific mutational profiles. METHODS We conducted targeted next-generation sequencing of 62 FM meningiomas from three international institutions, covering all relevant meningioma genes (AKT1, KLF4, NF2, POLR2A, PIK3CA, SMO, and TRAF7). Additionally, we retrospectively collected and evaluated patient and tumor characteristics, including age, sex, radiological features, and tumor location. RESULTS Our cohort consisted of 46 female and 16 male patients. Clinically significant driver mutations were detected in 58 patients (93.5%). The most commonly observed alteration was TRAF7 mutations (n=26, 41.9%), followed by AKT1(E17K) mutations (n=19, 30.6%). Both mutations were significantly associated with an anterolateral tumor location relative to the brainstem (p=0.0078). Tumors harboring these mutations predominantly (89.3%) displayed meningiothelial histology. NF2 mutations were present in 11 cases (17.7%) and were associated with posterior tumor location, in contrast to tumors with TRAF7 and AKT1(E17K) mutations. Other common mutations in FM meningiomas included POLR2A mutations (n=8, 12.9%), KLF4 mutations (n=7, 11.6%), and PIK3CA mutations (n=3, 4.8%). These mutations exclusively occurred in female patients and showed no significant correlation with specific tumor locations. Eight tumors exhibited intratumoral calcification which was significantly more frequent in NF2-mutant compared with AKT1-mutant FM meningiomas (p=0.047). CONCLUSIONS Our findings provide important insights into the molecular genetics and clinicopathological characteristics of FM meningiomas. The identification of specific genetic alterations associated with tumor location, calcification, histology, and sex at diagnosis may have implications for personalized treatment strategies in the future.