Advances in meningioma genomics, proteomics, and epigenetics: insights into biomarker identification and targeted therapies

Nazem, Ahmad; Ruzevick, Jacob; Ferreira, Manuel

doi:10.18632/oncotarget.27841

Cited by 17 publications

(17 citation statements)

References 69 publications

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“…Notably, in a subset of our patients where tissue was available for genomic sequencing, mutations in NF2 and BAP1 were more common in secondary progressive tumors as compared to de novo tumors, which is consistent with prior reports [25]. Sequencing did not reveal any mutations within AKT1 or KLF4.…”

Section: Discussionsupporting

confidence: 91%

“…Taken as a whole, lower grade meningioma tumorigenesis has been shown to be related to mutations in NF2, TRAF7, KLF4, AKT1, BAP 1, and SMO as well as germline mutations in SMARCB1, SMARCE1, and SUFU [21][22][23][24]. In addition, these mutations are associated with tumorigenesis at specific locations.For example, tumors with NF2 mutations typically localize to the convexity or posterior fossa skull base while tumors with SMO mutations are specific for the olfactory groove and planum sphenoidale [25].…”

Section: Discussionmentioning

confidence: 99%

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WHO grade III meningioma: De novo tumors show improved progression free survival as compared to secondary progressive tumors

Ruzevick

Gibson

Tatman

et al. 2021

Journal of Clinical Neuroscience

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Emerging evidence suggest WHO grade III meningiomas that arise de novo as opposed to dedifferentiating from a lower grade may harbor differing prognoses. To investigate this, a single institution retrospective analysis of prospectively acquired patients between 1999 and 2018 was performed. Clinical data and radiographic parameters were reviewed to calculate progression free survival and overall survival in patients undergoing microsurgical resection. Next generation targeted sequencing of meningioma associated genes was performed on 11 tumors. Eighteen patients were identified as undergoing surgical resection of WHO grade III meningioma. Nine patients (50%) had de novo arising tumors and nine patients had secondary progressive tumors. To compare outcomes, only those patients undergoing gross total resection (Simpson grade I) were included for survival analysis. There was an improvement in median progression free survival for de novo resected tumors as compared to secondary progressive tumors (p = 0.02). Median overall survival for patients with de novo tumors was not statistically improved compared to that of secondary progressive tumors (p = 0.22). Next generation sequencing of targeted genes (NF2, BAP1, TRAF7, KLF4, SMO and AKT) revealed 5/11 tumors containing mutations in the NF2 gene, 2/11 containing BAP1 mutations, and a single tumor containing mutations in both NF2 and TRAF7. More mutations in NF2 and BAP1 were seen in the secondary progressive tumors.In conclusion, patients undergoing gross total resection for de novo arising grade III meningiomas showed improved progression free survival, though similar overall survival, as compared to those patients with secondary progressive tumors. Further studies focused on tumor associated genes and other associated risk factors are needed to improve risk-stratification.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

WHO grade III meningioma: De novo tumors show improved progression free survival as compared to secondary progressive tumors

Ruzevick

Gibson

Tatman

et al. 2021

Journal of Clinical Neuroscience

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“…A tumor suppressor, NF2 encodes a cytoskeleton scaffold protein involved in cell proliferation and apoptosis. Aggressive NF2 -mutated meningiomas acquire chromosomal instability or co-mutation in another tumor suppressor gene, SMARCB1 [ 13 ]. Most somatic NF2 mutations are in solitary, sporadic meningiomas, however, they can occur in radiation-induced and multiple meningiomas [ 14 ].…”

Section: Genomic Landscape Of Sporadic Meningiomasmentioning

confidence: 99%

The integrated multiomic diagnosis of sporadic meningiomas: a review of its clinical implications

et al. 2021

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Introduction Meningiomas are generally considered “benign,” however, these tumors can demonstrate variability in behavior and a surprising aggressiveness with elevated rates of recurrence. The advancement of next-generation molecular technologies have led to the understanding of the genomic and epigenomic landscape of meningiomas and more recent correlations with clinical characteristics and behavior. Methods Based on a thorough review of recent peer-reviewed publications (PubMed) and edited texts, we provide a molecular overview of meningiomas with a focus on relevant clinical implications. Results The identification of specific somatic driver mutations has led to the classification of several major genomic subgroups, which account for more than 80% of sporadic meningiomas, and can be distinguished using noninvasive clinical variables to help guide management decisions. Other somatic genomic modifications, including non-coding alterations and copy number variations, have also been correlated with tumor characteristics. Furthermore, epigenomic modifications in meningiomas have recently been described, with DNA methylation being the most widely studied and potentially most clinically relevant. Based on these molecular insights, several clinical trials are currently underway in an effort to establish effective medical therapeutic options for meningioma. Conclusion As we enhance our multiomic understanding of meningiomas, our ability to care for patients with these tumors will continue to improve. Further biological insights will lead to additional progress in precision medicine for meningiomas.

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“…Moreover, Kristin Huntoon et al reviewed clinicopathological and molecular aspects in meningioma. While there are currently no good adjuvant chemotherapeutic agents available, recent advances in the genomic and epigenomic landscape of meningiomas are being explored for potential targeted therapy for meningioma (7,8). Shao et al reviewed advances in chromosomal variations and molecular mechanisms involved in the progression of meningioma, and highlighted the association with malignant biological behavior including cell proliferation, angiogenesis, increased invasiveness, and inhibition of apoptosis.…”

Section: Updated Reviews Of Meningiomamentioning

confidence: 99%

Editorial: Meningioma: From Basic Research to Clinical Translational Study

Ho¹

2021

Front. Oncol.

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Meningioma is thought to originate from arachnoidal cells in the central nervous system (CNS) and accounts for approximately 30% of all brain tumors (1). Most meningiomas are low grade benign brain tumors (such as fibroblastic meningioma and meningothelial meningioma), which belong to the World Health Organization (WHO) grade I and have a good prognosis after surgery. About 20% of meningiomas are high grade malignant brain tumors and belong to the WHO grade II (such as atypical meningioma) or WHO grade III (such as anaplastic meningioma) (2). Malignant meningiomas, sometimes may evolve from benign meningiomas, are more aggressive. They have an increased risk of recurrence after surgery and significant mortality rates. Currently, surgical resection combined with adjuvant radiotherapy is the main treatment strategy for malignant meningiomas, and no effective targeted chemotherapies have been developed (3-5).Thus, in this Research Topic (https://www.frontiersin.org/research-topics/12083/meningiomafrom-basic-research-to-clinical-translational-study), we collected more than 60 manuscripts discussing meningioma issues involving from basic research to clinical translational study, intend to deeply state those unresolved problems in meningioma. For example, its recurrence factors, how to improve the prognosis for malignant meningioma patients, what about the targeted chemotherapy for refractory meningioma? CLINICAL ASPECTS OF MENINGIOMAMeningiomas are diverse in intracranial locations and pathology, which are classified into three WHO grades and 15 histological subtypes. Sometimes meningiomas presented preferred intracranial locations, which may reflect potential biological features. In this meningioma issue collection, Sun et al. analyzed the preferred locations of meningioma according to different biological characteristics. Malignant meningiomas, compared to benign meningiomas, are more aggressive and have higher risk of recurrence after surgery. Clinical prognosis of meningioma patient is closely related to the WHO grades: patients with benign meningiomas have 5-year survival rates of 92%; however, the 5-year survival rates decrease to 78% in atypical meningiomas, and drop to 47% in anaplastic meningiomas. Currently, effective treatment for malignant meningiomas is still difficult (6). Here, we reviewed several manuscripts discussing meningioma treatment.

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Advances in meningioma genomics, proteomics, and epigenetics: insights into biomarker identification and targeted therapies

Cited by 17 publications

References 69 publications

WHO grade III meningioma: De novo tumors show improved progression free survival as compared to secondary progressive tumors

WHO grade III meningioma: De novo tumors show improved progression free survival as compared to secondary progressive tumors

The integrated multiomic diagnosis of sporadic meningiomas: a review of its clinical implications

Editorial: Meningioma: From Basic Research to Clinical Translational Study

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