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Genetic characterization and mutational profiling of foramen magnum meningiomas: a multi-institutional study.
Hua, Lingyang; Alkhatib, Majd; Fujio, Shingo; Alhasan, Boshr; Herold, Sylvia; Zeugner, Silke; Zolal, Amir; Hijazi, Mido M; Clark, Victoria E; Wakimoto, Hiroaki; Shankar, Ganesh M; Brastianos, Priscilla K; Barker, Frederick G; Cahill, Daniel P; Ren, Leihao; Eyüpoglu, Ilker Y; Gong, Ye; Schackert, Gabriele; Juratli, Tareq A.
Afiliación
  • Hua L; 1Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
  • Alkhatib M; 2Department of Neurosurgery, Division of Neuro-Oncology, Faculty of Medicine and Carl Gustav Carus University Hospital, Technische Universität Dresden, Germany.
  • Fujio S; 3Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
  • Alhasan B; 2Department of Neurosurgery, Division of Neuro-Oncology, Faculty of Medicine and Carl Gustav Carus University Hospital, Technische Universität Dresden, Germany.
  • Herold S; 4Department of Pathology, Carl Gustav Carus University Hospital, Technische Universität Dresden, Germany.
  • Zeugner S; 5Core Unit for Molecular Tumor Diagnostics (CMTD), National Center for Tumor Diseases (NCT/UCC), Dresden, Germany.
  • Zolal A; 4Department of Pathology, Carl Gustav Carus University Hospital, Technische Universität Dresden, Germany.
  • Hijazi MM; 5Core Unit for Molecular Tumor Diagnostics (CMTD), National Center for Tumor Diseases (NCT/UCC), Dresden, Germany.
  • Clark VE; 2Department of Neurosurgery, Division of Neuro-Oncology, Faculty of Medicine and Carl Gustav Carus University Hospital, Technische Universität Dresden, Germany.
  • Wakimoto H; 2Department of Neurosurgery, Division of Neuro-Oncology, Faculty of Medicine and Carl Gustav Carus University Hospital, Technische Universität Dresden, Germany.
  • Shankar GM; 6Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
  • Brastianos PK; 6Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
  • Barker FG; 6Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
  • Cahill DP; 7Department of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts; and.
  • Ren L; 6Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
  • Eyüpoglu IY; 6Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
  • Gong Y; 1Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
  • Schackert G; 2Department of Neurosurgery, Division of Neuro-Oncology, Faculty of Medicine and Carl Gustav Carus University Hospital, Technische Universität Dresden, Germany.
  • Juratli TA; 1Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
J Neurosurg ; 141(1): 72-78, 2024 Jul 01.
Article en En | MEDLINE | ID: mdl-38277657
ABSTRACT

OBJECTIVE:

Foramen magnum (FM) meningiomas pose significant surgical challenges and have high morbidity and mortality rates. This study aimed to investigate the distribution of clinically actionable mutations in FM meningiomas and identify clinical characteristics associated with specific mutational profiles.

METHODS:

The authors conducted targeted next-generation sequencing of 62 FM meningiomas from three international institutions, covering all relevant meningioma genes (AKT1, KLF4, NF2, POLR2A, PIK3CA, SMO, TERT promoter, and TRAF7). Patients with a radiation-induced meningioma or neurofibromatosis type 2 (NF2) were excluded from the study. Additionally, patient and tumor characteristics, including age, sex, radiological features, and tumor location, were retrospectively collected and evaluated.

RESULTS:

The study 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 (26, 41.9%), followed by AKT1E17K mutations (19, 30.6%). Both mutations were significantly associated with an anterolateral tumor location relative to the brainstem (p = 0.0078). NF2 mutations were present in 11 cases (17.7%) and were associated with posterior tumor location, in contrast to tumors with TRAF7 and AKT1E17K mutations. Other common mutations in FM meningiomas included POLR2A mutations (8, 12.9%; 6 POLR2AQ403K and 2 POLR2AH439_L440del), KLF4K409Q mutations (7, 11.3%), and PIK3CA mutations (4, 6.5%; 2 PIK3CAH1047R and 2 PIK3CAE545K). POLR2A and KLF4 mutations exclusively occurred in female patients and showed no significant association with specific tumor locations. All tumors harboring AKT1E17K and POLR2A mutations displayed meningothelial histology. Ten tumors exhibited intratumoral calcification, which was significantly more frequent in NF2-mutant compared with AKT1-mutant FM meningiomas (p = 0.047).

CONCLUSIONS:

These findings provide important insights into the molecular genetics and clinicopathological characteristics of FM meningiomas. The identification of specific genetic alterations associated with tumor location, volume, calcification, histology, and sex at diagnosis may have implications for personalized treatment strategies in the future.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neurofibromina 2 / Foramen Magno / Factor 4 Similar a Kruppel / Neoplasias Meníngeas / Meningioma / Mutación Tipo de estudio: Prognostic_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: J Neurosurg Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neurofibromina 2 / Foramen Magno / Factor 4 Similar a Kruppel / Neoplasias Meníngeas / Meningioma / Mutación Tipo de estudio: Prognostic_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: J Neurosurg Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos