Genomic Analysis of Posterior Fossa Meningioma Demonstrates Frequent AKT1 E17K Mutations in Foramen Magnum Meningiomas

Williams, Sally R.; Juratli, Tareq A.; Castro, Brandyn; Lazaro, Tyler; Gill, Corey M.; Nayyar, Naema; Strickland, Matthew R.; Babinski, Melanie; Johnstone, Sarah E.; Frosch, Matthew P.; Silverman, Ian M.; Ely, Heather A.; Kaplan, Alexander; D’Andrea, Megan R.; Bihun, Ivanna V.; Hoang, Kaitlin; Batchelor, Emily; Christiansen, Jason; Cahill, Daniel P.; Barker, Frederick G.; Brastianos, Priscilla K.

doi:10.1055/s-0038-1676821

Cited by 20 publications

(17 citation statements)

References 34 publications

(47 reference statements)

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“…Further, we did not find any differences between primary and recurrent tumors by specific driver mutation in regard to baseline characteristics (e.g., sex, location, grade of resection), though previous work has noted, for example, a tendency for non- NF2 variant tumors such as AKT1 and SMO to develop in skull base regions relative to CPF regions [25, 33, 36]. However, several driver mutations were associated with specific tumor features including WHO grade.…”

Section: Discussioncontrasting

confidence: 67%

Comparative genomic analysis of driver mutations in matched primary and recurrent meningiomas

et al. 2019

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A significant proportion of low-grade WHO grade I and higher-grade WHO grade II or III meningiomas are at risk to develop post-resection recurrence. Though recent studies investigated genomic alterations within histological subtypes of meningiomas, few have compared genomic profiles of primary meningiomas matched to their recurrences. The present study aimed to identify oncogenic driver mutations that may indicate risk of meningioma recurrence and aggressive clinical course. Seventeen patients treated for low-grade ( n = 8) or high-grade ( n = 9) meningioma and underwent both primary and recurrent resection between 2007–2017 were reviewed. Tumor specimens ( n = 38) underwent genomic sequencing of known oncogenic driver mutations. Primary and recurrent tumors were compared using matched-pair analyses for mutational associations with clinical outcomes including functional status, progression-free survival (PFS) and overall survival (OS). Most common driver mutations included POLE and NF2 . There was no enrichment for any driver mutation from primary to recurrent tumor specimen. NF2 mutant meningiomas were associated with larger tumor size (8-fold increase), presence of vasogenic edema, and higher mitotic proliferation on univariate and independently on multivariate regression (p’s < 0.05) after controlling for preoperative and tumor features. Tumors with POLE driver mutations were associated with decreased functional status at last postoperative follow-up ( p = 0.022) relative to presentation. Mutation status was not associated with PFS or OS on multivariate Cox regression, but rather with grade of resection ( p = 0.046) for PFS. While primary and recurrent tumors exhibited similar driver mutations within patients, the identification of driver mutations associated with clinical outcomes is crucial for guiding potential targeted treatments in recurrent meningiomas.

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Section: Discussioncontrasting

confidence: 67%

Comparative genomic analysis of driver mutations in matched primary and recurrent meningiomas

et al. 2019

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“…TRAF7 mutations share anatomic locations with KLF4 and AKT1 mutations at the sphenoid wing and midline skull base, and anterior midline skull base, respectively [ 58 ]. AKT1 mutations also show localization in the spine and foramen magnum [ 47 , 89 ]. POLR2A mutations are preferentially located at the anterior skull base in the tuberculum sellae [ 84 ].…”

Section: Introductionmentioning

confidence: 99%

Meningioma: A Review of Epidemiology, Pathology, Diagnosis, Treatment, and Future Directions

2021

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Meningiomas are the most common intracranial tumor, making up more than a third of all primary central nervous system (CNS) tumors. They are mostly benign tumors that can be observed or preferentially treated with gross total resection that provides good outcomes. Meningiomas with complicated histology or in compromising locations has proved to be a challenge in treating and predicting prognostic outcomes. Advances in genomics and molecular characteristics of meningiomas have uncovered potential use for more accurate grading and prediction of prognosis and recurrence. With the study and detection of genomic aberrancies, specific biologic targets are now being trialed for possible management of meningiomas that are not responsive to standard surgery and radiotherapy treatment. This review summarizes current epidemiology, etiology, molecular characteristics, diagnosis, treatments, and current treatment trials.

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“…A recent large genetic analysis found high rates of NF-2 and POLR2A alterations in posterior fossa region meningiomas [ 53 ]. In addition to the anterior skull base, AKT1E17K mutations were also found in posterior fossa and specifically as many as 50% of foramen magnum meningiomas in one series [ 59 ]. Identifying genetic biomarkers for these difficult to treat tumors is especially important as this may lead to potential therapeutic targets for tumors that recur or are incompletely resected.…”

Section: Genetic Biomarkers and Tumor Locationmentioning

confidence: 99%

Genomic Biomarkers of Meningioma: A Focused Review

Pawloski

Fadel

Huang

et al. 2021

IJMS

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Meningiomas represent a phenotypically and genetically diverse group of tumors which often behave in ways that are not simply explained by their pathologic grade. The genetic landscape of meningiomas has become a target of investigation as tumor genomics have been found to impact tumor location, recurrence risk, and malignant potential. Additionally, targeted therapies are being developed that in the future may provide patients with personalized chemotherapy based on the genetic aberrations within their tumor. This review focuses on the most common genetic mutations found in meningiomas of all grades, with an emphasis on the impact on tumor location and clinically relevant tumor characteristics. NF-2 and the non-NF-2 family of genetic mutations are summarized in the context of low-grade and high-grade tumors, followed by a comprehensive discussion regarding the genetic and embryologic basis for meningioma location and phenotypic heterogeneity. Finally, targeted therapies based on tumor genomics currently in use and under investigation are reviewed and future avenues for research are suggested. The field of meningioma genomics has broad implications on the way meningiomas will be treated in the future, and is gradually shifting the way clinicians approach this diverse group of tumors.

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Genomic Analysis of Posterior Fossa Meningioma Demonstrates Frequent AKT1 E17K Mutations in Foramen Magnum Meningiomas

Cited by 20 publications

References 34 publications

Comparative genomic analysis of driver mutations in matched primary and recurrent meningiomas

Comparative genomic analysis of driver mutations in matched primary and recurrent meningiomas

Meningioma: A Review of Epidemiology, Pathology, Diagnosis, Treatment, and Future Directions

Genomic Biomarkers of Meningioma: A Focused Review

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