Multiplatform profiling of meningioma provides molecular insight and prioritization of drug targets for rational clinical trial design

Everson, Richard; Hashimoto, Yuichi; Freeman, Jacob; Hodges, Tiffany R.; Huse, Jason T.; Zhou, Shouhao; Xiu, Joanne; Spetzler, David; Sanai, Nader; Kim, Lyndon; Kesari, Santosh; Brenner, Andrew; Monte, Franco De; Heimberger, Amy B.; Raza, Shaan M.

doi:10.1007/s11060-018-2891-8

Cited by 19 publications

(26 citation statements)

References 54 publications

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“…Loss of the CDKN2A/CDNK2B locus on chromosome 9q is also a relatively common event during progression from grade II to III (16). Interestingly, recent efforts also identified a recurrent amplification of this locus, within grade I tumors (17). These data suggest that levels of p16 and p15, the proteins encoded by CDKN2A and CDKN2B, may hold prognostic significance and/or represent a promising therapeutic target.…”

Section: Cyotgeneticsmentioning

confidence: 89%

“…Several other individual amplifications in genes including, FGF3, ZNF217, ZNF331, CDK4, ERBB3, LRG5, MDM2, NACA, PTPN11, WIF1, PDCD1, TLX1, ARFRP1, GNAS, SS18L1, FoxA1, FGF6, and FGF10, have also been identified, though evolutionary analysis of these tumors reveals that SCNA likely precedes such driver mutations, leading to both inter-and intra-patient heterogeneity in mutational profiles (17). Interestingly, the identification of spatial heterogeneity among multiple tumors from the same patients, suggests that distinct microenvironments may influence tumor formation and growth (11).…”

Section: Cyotgeneticsmentioning

confidence: 99%

“…As high grade meningiomas are associated with rapid disease progression and poor prognosis as compared to low grade, recent efforts in next-generation sequencing have sought to identify prognostic biomarker to differentiate between tumors of varying grades, and those that may correlate with treatment response. With a low mutation rate (∼3.5 mutations per megabase) compared to other cancers (17), these efforts highlight the challenges in managing these heterogeneous tumors. Similar to cytogenetic analysis, these studies identified NF2 mutations as the predominant alteration in both spontaneous (∼60%) and Neurofibromatosis syndrome associated (∼40%) of tumors (16), at a frequency of 43% in low grade, and nearly 80% in high grade tumors (11).…”

Section: Nf2-mutated Meningiomamentioning

confidence: 99%

“…Within tumor cells, expression of PD-L1, the PD-1 receptor ligand, increases with WHO tumor grade (17,55,57,58). However, overall mRNA or protein levels, as analyzed by RT-PCR, ISH, IHC, and flow cytometry varies widely from study to study.…”

Section: Expression/immunoprofilingmentioning

confidence: 99%

“…However, overall mRNA or protein levels, as analyzed by RT-PCR, ISH, IHC, and flow cytometry varies widely from study to study. Du and colleagues report high levels of PD-L1 mRNA which correlated to protein expression levels, in ∼40% of grade I, 60% of grade II, and 77-88% of grade III meningiomas (55), while Everson and colleagues only identified PD-L1 in 25% of grade III cases, with no IHC expression detected in grade I or II cases (17). One potential source of these observed differences in PD-L1 expression may arise from the specific populations of cells analyzed.…”

Section: Expression/immunoprofilingmentioning

confidence: 99%

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Recent Advances in Meningioma Immunogenetics

2020

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Meningiomas are relatively common, and typically benign intracranial tumors, which in many cases can be cured by surgical resection. However, less prevalent, high grade meningiomas, grow quickly, and recur frequently despite treatment, leading to poor patient outcomes. Across tumor grades, subjective guidelines for histological analysis can preclude accurate diagnosis, and an insufficient understanding of recurrence risk can cloud the choice of optimal treatment. Improved diagnostic and prognostic markers capable of discerning between the 15 heterogeneous WHO recognized meningioma subtypes are necessary to improve disease management and identify new targeted drug treatments. In this review, we show the advances in molecular profiling and immunophenotyping of meningiomas, which may lead to the development of new personalized therapeutic strategies.

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Section: Cyotgeneticsmentioning

confidence: 89%

Section: Cyotgeneticsmentioning

confidence: 99%

Section: Nf2-mutated Meningiomamentioning

confidence: 99%

Section: Expression/immunoprofilingmentioning

confidence: 99%

Section: Expression/immunoprofilingmentioning

confidence: 99%

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Recent Advances in Meningioma Immunogenetics

2020

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Intracranial intricacies: Comprehensive analysis of rare skull base meningiomas—A single‐center case series

Nadeem,

Khan,

Habib

et al. 2023

Clinical Case Reports

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Key Clinical MessageThis study paper's main goal is to report rare cases of skull base meningiomas that exemplify the complexities of diagnosis, therapy, and postoperative care. By describing these rare cases, we hope to advance knowledge of the clinical signs, difficulties, and prognoses of skull base meningiomas in a challenging anatomical setting. In the posterior cranial fossa, our investigation reveals a unique example of skull base meningioma that involved numerous cranial nerves and complex vasculature. A variety of visual abnormalities were present in the patient's clinical presentations, highlighting the wide range of symptoms that these tumors might cause depending on their precise positions. These cases highlight the critical importance of preoperative imaging, including high‐resolution MRI and angiography, as well as the diagnostic difficulties these tumors pertain. By reporting these instances, our research adds to the body of knowledge about skull base meningiomas and offers insightful information about the nuances of their therapies. Our findings highlight the importance of individualized treatment plans, interdisciplinary cooperation, and the demand for continued study to better comprehend these convoluted tumors. Such studies are essential for advancing our knowledge of these enigmatic tumors, guiding clinical judgment, and eventually improving patient outcomes. These findings are important because they can fill information gaps, improve treatment plans, and encourage additional research in neuro‐oncology.AbstractThis study presents a series of three rare cases of skull base meningiomas, emphasizing the complexities in diagnosis, treatment, and postoperative care. The patients' clinical presentations and imaging highlighted the diverse symptoms and challenges associated with these tumors, found in intricate anatomical locations. The cases underscore the crucial role of preoperative high‐resolution imaging and angiography in diagnostic accuracy. Surgical intervention, guided by a multidisciplinary approach, is pivotal in managing these demanding cases. Histopathological examinations confirmed atypical meningiomas. The postoperative phases involved meticulous care to ensure optimal recovery and functional outcomes. Our findings contribute to the understanding of skull base meningiomas, emphasizing the need for personalized treatment plans and ongoing research to improve patient outcomes in neuro‐oncology.

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Emerging Meningioma Therapies II: Immunotherapies, Novel Radiotherapy Techniques, and Other Experimental Approaches

Gill

Brastianos

2020

Meningiomas

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Multiplatform profiling of meningioma provides molecular insight and prioritization of drug targets for rational clinical trial design

Abstract: If predicated on tumor expression, our data suggest that therapeutics directed toward NF2 and TOP2A could be considered for most meningioma patients.

Cited by 19 publications

References 54 publications

Recent Advances in Meningioma Immunogenetics

Recent Advances in Meningioma Immunogenetics

Intracranial intricacies: Comprehensive analysis of rare skull base meningiomas—A single‐center case series

Emerging Meningioma Therapies II: Immunotherapies, Novel Radiotherapy Techniques, and Other Experimental Approaches

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