Article
AKT1E17K and NF2mutations are the main driver events in spinal meningiomas and are associated with distinct tumour features
AKT1E17K- und NF2-Mutationen sind die Hauptereignisse bei spinalen Meningeomen und sind mit unterschiedlichen Tumormerkmalen assoziiert
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Authors
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Majd Alkhatib
- Carl Gustav Carus Universitätsklinikum, TU Dresden, Klinik und Poliklinik für Neurochirurgie, Dresden, Deutschland
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Lingyang Hua
- Fudan University, Neurosurgery, Shanghai, China, Volksrepublik
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Dino Podlesek
- Carl Gustav Carus Universitätsklinikum, TU Dresden, Klinik und Poliklinik für Neurochirurgie, Dresden, Deutschland
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Leila Günther
- Technische Universität Dresden, Medizin, Dresden, Deutschland
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Ye Gong
- Fudan University, Neurosurgery, Shanghai, China, Volksrepublik
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Matthias Kirsch
- Asklepios Kliniken Schildautal, Klinik für Neurochirurgie, Seesen, Deutschland
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Gabriele Schackert
- Carl Gustav Carus Universitätsklinikum, TU Dresden, Klinik und Poliklinik für Neurochirurgie, Dresden, Deutschland
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Tareq Juratli
- Carl Gustav Carus Universitätsklinikum, TU Dresden, Klinik und Poliklinik für Neurochirurgie, Dresden, Deutschland
| Published: | May 25, 2022 |
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Outline
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Objective: Meningiomas represent about one-third of all spinal tumors. To date, few is known about the molecular profile of spinal meningiomas (SM) and its clinical impact. In this study, we correlate tumor features with the molecular status in a well-characterized cohort of 50 SM patients.
Methods: SM samples from 39 females and 11 males were collected. We preformed Next Generation Sequencing using an assay that covers a large number of frequently mutated genes in meningiomas including AKT1, KLF4, NF2, PIK3CA/PIK3R1, POLR2A, SMARCB1, SMO, SUFU, TRAF7, and the TERT promoter. Furthermore, we correlated clinical and imaging data with the molecular tumor status.
Results: AKT1 mutations were detected in 15 (30%) and NF2 mutations in 32 (64%) patients. In three cases (6%) no known driver mutations were found. NF2-mutant meningiomas occurred significantly more frequently in female patients (n= 30, 94%) than AKT1-mutant tumors (n= 7, p= 0.0006). A tumor location in the thoracic spine was significantly more common in NF2-mutant meningiomas (n= 25) than in their AKT1-mutant counterparts (n= 4, p= 0.0012). In contrast, meningiomas harboring an AKT1 mutation were predominantly located in the cervical spine (n= 11, 73.3%). Notably, 87% of AKT1-mutant meningiomas (n= 13) and 28% of NF2-mutant meningiomas (n= 14) arose ventrally to the spinal cord (p= 0.0101). NF2-mutant meningiomas developed mainly in dorsal location to the spinal cord (n= 18, 56.2%). The histologic subtype of NF2-mutant meningiomas was variable (7 meningothelial, 14 psammomatous, 3 transitional, 5 fibrous), while all but one meningiomas harboring an AKT1 mutation showed a meningiothelial histology (93.3%, p= 0.0001). Finally, none of the AKT1-mutant meningiomas showed calcifications in the MRI, whereas all calcified meningiomas (n= 17) were NF2-mutant (p= 0.0002).
Conclusion: AKT1 and NF2 mutations represent the main driver events in SM and are associated with distinct tumor features. AKT1-mutant meningiomas occur predominantly in male patients, originate in the cervical spine ventrally to the spinal cord, are almost exclusively associated with a meningothelial histology and exhibit no calcifications on MR imaging. NF2-mutant meningiomas are mainly representative in female patients, arise most frequently in the thoracic spine dorsally to the spinal cord, show variable histologic subtypes and are commonly calcified.
