Molecular Landscape and Clinical Correlates of Olfactory Groove Meningiomas: A Multi-institutional Study

Objective: This study investigates the relationship between the clinical and radiological characteristics of olfactory groove meningiomas (OGMs) and their molecular profiles. It emphasizes the identification of oncogenic mutations through radiographic analysis.

Methods: We performed targeted next-generation and whole-genome sequencing on 123 OGM samples collected from four international institutions, focusing on known meningioma-driver genes. We compared the molecular data with the clinical and radiographic features of the tumors. Patient and tumor data, including age, sex, radiological features, and overall survival, were retrospectively collected and analyzed.

Results: The study cohort comprised 90 females (73%) and 33 males (27%), with median age at diagnosis of 57 years (range: 25–87years). The majority of tumors (88.6%, n = 109) were classified as WHO grade 1 meningioma. However, only one NF2 mutation was identified across the cohort, highlighting the distinct molecular etiology of these tumors compared to convexity meningiomas. Known driver mutations were found in 86.2% of patients (n = 106). The most common mutations were found in the SMOL412F/W535L/SUFU and AKT1E17K genes, each present in 36 cases (29.3%), followed by mutations in PIK3CA/PIK3R1 ([19 cases, 15.4%], [14 PIK3CA and 5 PIK3R1]), TRAF7 alone (7 cases, 5.7%), POLR2AQ403K (4 cases, 3.3%), and TRAF7/KLF4K409Q (3 cases, 2.4%). In 17 patients (13.8%), no known meningioma driver mutations were detectable (wild-type group). SMO and AKT1 mutations were significantly associated with the meningothelial subtype (p = 0.0005). Within molecular subgroups, the youngest median age were patients with AKT1 mutations (median age: 51years) and the oldest in the TRAF7 only mutant group (median: 66 years, range: 28–76 years). Median tumor volume at diagnosis was 18.04 cm³. Among tumors with known driver mutations, TRAF7 only mutant OGMs presented with the largest median volume (29.5 cm³), followed by SMO-mutant OGMs (19.5 cm³), whereas AKT1 and TRAF7/KLF4 mutations were associated with the smallest tumor volumes (7.5 and 4.9 cm³, respectively). SMO-mutant tumors demonstrated significantly larger volumes compared to both AKT1 mutant (p = 0.021) and TRAF7/KLF4 mutant tumors (p = 0.002). Tumor-associated hyperostosis of the sphenoid planum was common (58.5%), led by PIK3CA/PIK3R1, SMO, and wild-type groups (73.6, 72.2, and 70.5%, respectively), compared to a notably lower rate in AKT1 mutant tumors (25%) (p < 0.001). Tumor invasion of the ethmoid sinuses occurred in 25 cases (20.3%), most frequently in the TRAF7 only mutant OGMs (42.8%), followed by PIK3CA/PIK3R1 mutant (31.5%) and wild-type OGMs (23.5%). The mean progression-free survival was 144.4 months (95% confidence interval [CI]: 123.8–165 months). Within mutation-defined subgroups, patients with SMO mutations had significantly shorter progression-free survival (mean: 95.7 months, 95% CI: 76.4–115.1 months), identifying a tumor type that may benefit from adjuvant treatment after subtotal resection.

Conclusion: This comprehensive study provides significant insights into the genetic underpinnings and clinical behaviors as well as radiological features of OGMs. It also highlights the prognostic implications of specific mutations: SMO mutations were linked with shorter PFS, whereas AKT1 mutations were associated with longer survival and smaller tumor volumes, suggesting a possible biomarker for prognosis and therapeutic targeting. These findings support the use of a molecularly-guided strategy in diagnosing, managing, and predicting outcomes for OGMs, highlighting the importance of genetic profiling in routine clinical practice to improve patient results.

Publication History

Article published online:
07 February 2025