Materiały źródłowe

• #1 Molecular Mechanism and Approach in Progression of Meningioma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7518150/

  Meningioma is the most common tumor of the central nervous system, most of which is benign. Even after complete resection, a high rate of recurrence of meningioma is observed. From in-depth study of its pathogenesis, it has been found that a number of chromosomal variations and abnormal molecular signals are closely related to the occurrence and development of malignancy in meningioma, which may provide the theoretical basis and potential direction for accurate and targeted treatment. […] Previous studies have identified multiple molecular targets and genetic alterations that contribute to its progression, including those related to cell proliferation, increased invasiveness, angiogenesis, and inhibition of apoptosis. These molecular targets may be targeted in future to improve the therapeutic effect. Here, we summarize the molecular mechanisms that drive the biological behavior and relative medical treatment of meningioma.

• #2 Molecular pathogenesis of meningiomas – PubMed

  https://pubmed.ncbi.nlm.nih.gov/15674477/

  Meningiomas are common central nervous system tumors that originate from the meningeal coverings of the brain and the spinal cord. […] Current data indicate that meningioma initiation is closely linked to the inactivation of one or more members of the highly conserved protein 4.1 superfamily, including the neurofibromatosis type 2 gene product merlin/schwannomin, protein 4.IB (DAL-1) and protein 4.1R. […] A better understanding of the molecular mechanisms involved in meningioma pathogenesis may not only lead to the identification of novel diagnostic and prognostic marker but will also facilitate the development of new pathogenesis-based therapeutic strategies.

• #3 Meningioma: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1156552-overview

  Meningiomas may occur intracranially or within the spinal canal. They are thought to arise from arachnoidal cap cells, which reside in the arachnoid layer covering the surface of the brain. […] Meningiomas produce their symptoms by several mechanisms. They may cause symptoms by irritating the underlying cortex, compressing the brain or the cranial nerves, producing hyperostosis and/or invading the overlying soft tissues, or inducing vascular injuries to the brain. […] The problem of classifying meningioma is that arachnoidal cells may express both mesenchymal and epithelial characteristics. Other mesodermal structures also may give rise to similar tumors (eg, hemangiopericytomas or sarcomas). The classification of all of these tumors together is controversial. The current trend is to separate unequivocal meningiomas from other less well-defined neoplasms. Undoubtedly, advances in molecular biology will allow scientists to determine the exact genomic aberration responsible for each specific neoplasm.

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

  https://www.mdpi.com/2227-9059/9/3/319

  Meningiomas are the most common primary central nervous system (CNS) tumors. They are usually benign, slow growing neoplasms that are thought to arise from meningothelial (arachnoid) cells (MECs). 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. […] Meningothelial cells (MECs) are a cellular component of the pia mater, arachnoid mater, and the trabeculae and septae of the subarachnoidal space. They make up a monolayer covering of the meninges and are connected via tight junctions, gap junctions, and desmosomes, providing an interface between neuronal tissue and the cerebrospinal fluid (CSF). MECs also play a significant role in immunological processes and the maintenance of homeostasis and host defense in the CSF.

• #5 Molecular Mechanism and Approach in Progression of Meningioma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7518150/

  Meningioma is the most common tumor of the central nervous system, most of which is benign. Even after complete resection, a high rate of recurrence of meningioma is observed. From in-depth study of its pathogenesis, it has been found that a number of chromosomal variations and abnormal molecular signals are closely related to the occurrence and development of malignancy in meningioma, which may provide the theoretical basis and potential direction for accurate and targeted treatment. […] Previous studies have identified multiple molecular targets and genetic alterations that contribute to its progression, including those related to cell proliferation, increased invasiveness, angiogenesis, and inhibition of apoptosis. These molecular targets may be targeted in future to improve the therapeutic effect. Here, we summarize the molecular mechanisms that drive the biological behavior and relative medical treatment of meningioma.

• #6 Molecular Mechanism and Approach in Progression of Meningioma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7518150/

  Meningioma is the most common tumor of the central nervous system, most of which is benign. Even after complete resection, a high rate of recurrence of meningioma is observed. From in-depth study of its pathogenesis, it has been found that a number of chromosomal variations and abnormal molecular signals are closely related to the occurrence and development of malignancy in meningioma, which may provide the theoretical basis and potential direction for accurate and targeted treatment. […] Previous studies have identified multiple molecular targets and genetic alterations that contribute to its progression, including those related to cell proliferation, increased invasiveness, angiogenesis, and inhibition of apoptosis. These molecular targets may be targeted in future to improve the therapeutic effect. Here, we summarize the molecular mechanisms that drive the biological behavior and relative medical treatment of meningioma.

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

  https://www.mdpi.com/2227-9059/9/3/319

  Meningiomas are the most common primary central nervous system (CNS) tumors. They are usually benign, slow growing neoplasms that are thought to arise from meningothelial (arachnoid) cells (MECs). 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. […] Meningothelial cells (MECs) are a cellular component of the pia mater, arachnoid mater, and the trabeculae and septae of the subarachnoidal space. They make up a monolayer covering of the meninges and are connected via tight junctions, gap junctions, and desmosomes, providing an interface between neuronal tissue and the cerebrospinal fluid (CSF). MECs also play a significant role in immunological processes and the maintenance of homeostasis and host defense in the CSF.

• #8 Molecular Mechanism and Approach in Progression of Meningioma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7518150/

  The most common chromosomal abnormality in meningioma is in chromosome 22, observed in 40-70% of grade I meningioma. Beyond the loss of chromosome 22, few other chromosomal abnormalities have been observed in benign meningioma. In an analysis of chromosome 22 in 44 sporadic meningiomas, researchers found that in 43 cases, all or part of the chromosome had been deleted, the majority of deletions occurring in the neurofibromatosis type 2 (NF2) region, suggesting that the mutation on NF2 leads to the occurrence of meningioma. […] Atypical and anaplastic meningioma exhibit a greater number of chromosomal abnormalities than benign meningioma, but the frequency of the NF2 gene mutations is almost the same as in benign meningioma, indicating that NF2 may not be related to the progression of meningioma.

• #9 Molecular Mechanism and Approach in Progression of Meningioma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7518150/

  The most common chromosomal abnormality in meningioma is in chromosome 22, observed in 40-70% of grade I meningioma. Beyond the loss of chromosome 22, few other chromosomal abnormalities have been observed in benign meningioma. In an analysis of chromosome 22 in 44 sporadic meningiomas, researchers found that in 43 cases, all or part of the chromosome had been deleted, the majority of deletions occurring in the neurofibromatosis type 2 (NF2) region, suggesting that the mutation on NF2 leads to the occurrence of meningioma. […] Atypical and anaplastic meningioma exhibit a greater number of chromosomal abnormalities than benign meningioma, but the frequency of the NF2 gene mutations is almost the same as in benign meningioma, indicating that NF2 may not be related to the progression of meningioma.

• #10 Molecular Mechanism and Approach in Progression of Meningioma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7518150/

  The most common chromosomal abnormality in meningioma is in chromosome 22, observed in 40-70% of grade I meningioma. Beyond the loss of chromosome 22, few other chromosomal abnormalities have been observed in benign meningioma. In an analysis of chromosome 22 in 44 sporadic meningiomas, researchers found that in 43 cases, all or part of the chromosome had been deleted, the majority of deletions occurring in the neurofibromatosis type 2 (NF2) region, suggesting that the mutation on NF2 leads to the occurrence of meningioma. […] Atypical and anaplastic meningioma exhibit a greater number of chromosomal abnormalities than benign meningioma, but the frequency of the NF2 gene mutations is almost the same as in benign meningioma, indicating that NF2 may not be related to the progression of meningioma.

• #11 The molecular genetics and tumor pathogenesis of meningiomas and the future directions of meningioma treatments in: Neurosurgical Focus Volume 30 Issue 5 (2011) Journals

  https://thejns.org/focus/view/journals/neurosurg-focus/30/5/2011.2.focus1116.xml

  Meningiomas are mostly benign, slow-growing tumors of the CNS that originate from arachnoidal cap cells. While monosomy 22 is the most frequent genetic abnormality found in meningiomas, a multitude of other aberrant chromosomal alterations, signaling pathways, and growth factors have been implicated in its pathogenesis. Losses on 22q12.2, a region encoding the tumor suppressor gene merlin, represent the most common genetic alterations in early meningioma formation. Malignant meningioma progression, however, is associated with more complex karyotypes and greater genetic instability. Cytogenetic studies of atypical and anaplastic meningiomas revealed gains and losses on chromosomes 9, 10, 14, and 18, with amplifications on chromosome 17. However, the specific gene targets in a majority of these chromosomal abnormalities remain elusive.

• #12 The molecular genetics and tumor pathogenesis of meningiomas and the future directions of meningioma treatments in: Neurosurgical Focus Volume 30 Issue 5 (2011) Journals

  https://thejns.org/focus/view/journals/neurosurg-focus/30/5/2011.2.focus1116.xml

  Meningiomas are mostly benign, slow-growing tumors of the CNS that originate from arachnoidal cap cells. While monosomy 22 is the most frequent genetic abnormality found in meningiomas, a multitude of other aberrant chromosomal alterations, signaling pathways, and growth factors have been implicated in its pathogenesis. Losses on 22q12.2, a region encoding the tumor suppressor gene merlin, represent the most common genetic alterations in early meningioma formation. Malignant meningioma progression, however, is associated with more complex karyotypes and greater genetic instability. Cytogenetic studies of atypical and anaplastic meningiomas revealed gains and losses on chromosomes 9, 10, 14, and 18, with amplifications on chromosome 17. However, the specific gene targets in a majority of these chromosomal abnormalities remain elusive.

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

  https://www.mdpi.com/2227-9059/9/3/319

  Advances in molecular techniques over the last decade that include genomic and epigenomic data associated with meningiomas have been used to identify genetic biomarkers that may predict tumor behavior and prognosis. […] Chromosomal instability has repeatedly been shown to be one of the most frequent molecular alterations for tumor recurrence and prognosis. Accumulation of cytogenetic aberrations correlates with increasing tumor grades and aggressiveness, with higher-grade (atypical and anaplastic) meningiomas demonstrating an increasingly complex cytogenetic profile compared to benign meningiomas. […] While the majority of meningiomas occurs sporadically, there are many rare familial syndromes that increase the risk of developing these tumors. While exact molecular mechanisms have yet to be elucidated, these familial syndromes might provide insight behind sporadic meningioma tumorigenesis and implications for management.

• #14 Molecular pathogenesis of meningiomas – PubMed

  https://pubmed.ncbi.nlm.nih.gov/15674477/

  Meningiomas are common central nervous system tumors that originate from the meningeal coverings of the brain and the spinal cord. […] Current data indicate that meningioma initiation is closely linked to the inactivation of one or more members of the highly conserved protein 4.1 superfamily, including the neurofibromatosis type 2 gene product merlin/schwannomin, protein 4.IB (DAL-1) and protein 4.1R. […] A better understanding of the molecular mechanisms involved in meningioma pathogenesis may not only lead to the identification of novel diagnostic and prognostic marker but will also facilitate the development of new pathogenesis-based therapeutic strategies.

• #15 The Role of Merlin/NF2 Loss in Meningioma Biology

  https://www.mdpi.com/2072-6694/11/11/1633

  Mutations in the neurofibromin 2 (NF2) gene were among the first genetic alterations implicated in meningioma tumorigenesis, based on analysis of neurofibromatosis type 2 (NF2) patients who not only develop vestibular schwannomas but later have a high incidence of meningiomas. […] The early recognition of the crucial role of NF2 mutations in the pathogenesis of the majority of meningiomas has not yet translated into useful clinical insights, due to the complexity of merlin’s many interacting partners and signaling pathways. […] Next-generation sequencing studies and increasingly sophisticated NF2-deletion-based in vitro and in vivo models have helped elucidate the consequences of merlin loss in meningioma pathogenesis. […] The NF2 gene product, merlin, is a tumor suppressor that is thought to link the actin cytoskeleton with plasma membrane proteins and mediate contact-dependent inhibition of proliferation.

• #16 The Role of Merlin/NF2 Loss in Meningioma Biology

  https://www.mdpi.com/2072-6694/11/11/1633

  Mutations in the neurofibromin 2 (NF2) gene were among the first genetic alterations implicated in meningioma tumorigenesis, based on analysis of neurofibromatosis type 2 (NF2) patients who not only develop vestibular schwannomas but later have a high incidence of meningiomas. […] The early recognition of the crucial role of NF2 mutations in the pathogenesis of the majority of meningiomas has not yet translated into useful clinical insights, due to the complexity of merlin’s many interacting partners and signaling pathways. […] Next-generation sequencing studies and increasingly sophisticated NF2-deletion-based in vitro and in vivo models have helped elucidate the consequences of merlin loss in meningioma pathogenesis. […] The NF2 gene product, merlin, is a tumor suppressor that is thought to link the actin cytoskeleton with plasma membrane proteins and mediate contact-dependent inhibition of proliferation.

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

  https://www.mdpi.com/2227-9059/9/3/319

  NF2 is the most common and well-known familial syndrome associated with meningioma risk. NF2 is caused by a germline mutation of the NF2 gene on chromosome 22q12 and is inherited in an autosomal dominant pattern. Over 50% of NF2 patients will develop at least one intracranial meningioma in their lifetime. […] In the 1990s, the NF2 gene was discovered to be a major driver of meningioma development. NF2 is a tumor suppressor gene located on chromosome 22q12 that encodes the Merlin protein. Merlin is a scaffold protein that belongs to the BAND 4.1 FERM gene family. Loss of NF2 can activate oncogenic pathways, including Ras/mitogen-activated protein kinase, Notch, phosphoinositide 3-kinase (PI3K)/AKT, Hippo, and mammalian target of rapamycin (mTOR). […] Recent genomic studies of meningiomas have elucidated a rich array of recurrent non NF2 mutations, typically in TNF receptor-associated factor 7 (TRAF7), Kruppel-like factor 4 (KLF4), v-Akt murine thymoma viral oncogene homolog 1 (AKT1), RNA polymerase II subunit A (POLR2A), Telomerase reverse transcriptase (TERT), smoothened/frizzled class receptor (SMO), and Phosphadidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). Non-NF2 mutations are frequently identified in grade I tumors and are genomically stable, with the absence of large-scale chromosomal amplifications or deletions.

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

  https://www.mdpi.com/2227-9059/9/3/319

  NF2 is the most common and well-known familial syndrome associated with meningioma risk. NF2 is caused by a germline mutation of the NF2 gene on chromosome 22q12 and is inherited in an autosomal dominant pattern. Over 50% of NF2 patients will develop at least one intracranial meningioma in their lifetime. […] In the 1990s, the NF2 gene was discovered to be a major driver of meningioma development. NF2 is a tumor suppressor gene located on chromosome 22q12 that encodes the Merlin protein. Merlin is a scaffold protein that belongs to the BAND 4.1 FERM gene family. Loss of NF2 can activate oncogenic pathways, including Ras/mitogen-activated protein kinase, Notch, phosphoinositide 3-kinase (PI3K)/AKT, Hippo, and mammalian target of rapamycin (mTOR). […] Recent genomic studies of meningiomas have elucidated a rich array of recurrent non NF2 mutations, typically in TNF receptor-associated factor 7 (TRAF7), Kruppel-like factor 4 (KLF4), v-Akt murine thymoma viral oncogene homolog 1 (AKT1), RNA polymerase II subunit A (POLR2A), Telomerase reverse transcriptase (TERT), smoothened/frizzled class receptor (SMO), and Phosphadidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). Non-NF2 mutations are frequently identified in grade I tumors and are genomically stable, with the absence of large-scale chromosomal amplifications or deletions.

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

  https://www.mdpi.com/2227-9059/9/3/319

  NF2 is the most common and well-known familial syndrome associated with meningioma risk. NF2 is caused by a germline mutation of the NF2 gene on chromosome 22q12 and is inherited in an autosomal dominant pattern. Over 50% of NF2 patients will develop at least one intracranial meningioma in their lifetime. […] In the 1990s, the NF2 gene was discovered to be a major driver of meningioma development. NF2 is a tumor suppressor gene located on chromosome 22q12 that encodes the Merlin protein. Merlin is a scaffold protein that belongs to the BAND 4.1 FERM gene family. Loss of NF2 can activate oncogenic pathways, including Ras/mitogen-activated protein kinase, Notch, phosphoinositide 3-kinase (PI3K)/AKT, Hippo, and mammalian target of rapamycin (mTOR). […] Recent genomic studies of meningiomas have elucidated a rich array of recurrent non NF2 mutations, typically in TNF receptor-associated factor 7 (TRAF7), Kruppel-like factor 4 (KLF4), v-Akt murine thymoma viral oncogene homolog 1 (AKT1), RNA polymerase II subunit A (POLR2A), Telomerase reverse transcriptase (TERT), smoothened/frizzled class receptor (SMO), and Phosphadidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). Non-NF2 mutations are frequently identified in grade I tumors and are genomically stable, with the absence of large-scale chromosomal amplifications or deletions.

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

  https://www.mdpi.com/2227-9059/9/3/319

  NF2 is the most common and well-known familial syndrome associated with meningioma risk. NF2 is caused by a germline mutation of the NF2 gene on chromosome 22q12 and is inherited in an autosomal dominant pattern. Over 50% of NF2 patients will develop at least one intracranial meningioma in their lifetime. […] In the 1990s, the NF2 gene was discovered to be a major driver of meningioma development. NF2 is a tumor suppressor gene located on chromosome 22q12 that encodes the Merlin protein. Merlin is a scaffold protein that belongs to the BAND 4.1 FERM gene family. Loss of NF2 can activate oncogenic pathways, including Ras/mitogen-activated protein kinase, Notch, phosphoinositide 3-kinase (PI3K)/AKT, Hippo, and mammalian target of rapamycin (mTOR). […] Recent genomic studies of meningiomas have elucidated a rich array of recurrent non NF2 mutations, typically in TNF receptor-associated factor 7 (TRAF7), Kruppel-like factor 4 (KLF4), v-Akt murine thymoma viral oncogene homolog 1 (AKT1), RNA polymerase II subunit A (POLR2A), Telomerase reverse transcriptase (TERT), smoothened/frizzled class receptor (SMO), and Phosphadidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). Non-NF2 mutations are frequently identified in grade I tumors and are genomically stable, with the absence of large-scale chromosomal amplifications or deletions.

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

  https://www.mdpi.com/2227-9059/9/3/319

  NF2 is the most common and well-known familial syndrome associated with meningioma risk. NF2 is caused by a germline mutation of the NF2 gene on chromosome 22q12 and is inherited in an autosomal dominant pattern. Over 50% of NF2 patients will develop at least one intracranial meningioma in their lifetime. […] In the 1990s, the NF2 gene was discovered to be a major driver of meningioma development. NF2 is a tumor suppressor gene located on chromosome 22q12 that encodes the Merlin protein. Merlin is a scaffold protein that belongs to the BAND 4.1 FERM gene family. Loss of NF2 can activate oncogenic pathways, including Ras/mitogen-activated protein kinase, Notch, phosphoinositide 3-kinase (PI3K)/AKT, Hippo, and mammalian target of rapamycin (mTOR). […] Recent genomic studies of meningiomas have elucidated a rich array of recurrent non NF2 mutations, typically in TNF receptor-associated factor 7 (TRAF7), Kruppel-like factor 4 (KLF4), v-Akt murine thymoma viral oncogene homolog 1 (AKT1), RNA polymerase II subunit A (POLR2A), Telomerase reverse transcriptase (TERT), smoothened/frizzled class receptor (SMO), and Phosphadidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). Non-NF2 mutations are frequently identified in grade I tumors and are genomically stable, with the absence of large-scale chromosomal amplifications or deletions.

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

  https://www.mdpi.com/2227-9059/9/3/319

  NF2 is the most common and well-known familial syndrome associated with meningioma risk. NF2 is caused by a germline mutation of the NF2 gene on chromosome 22q12 and is inherited in an autosomal dominant pattern. Over 50% of NF2 patients will develop at least one intracranial meningioma in their lifetime. […] In the 1990s, the NF2 gene was discovered to be a major driver of meningioma development. NF2 is a tumor suppressor gene located on chromosome 22q12 that encodes the Merlin protein. Merlin is a scaffold protein that belongs to the BAND 4.1 FERM gene family. Loss of NF2 can activate oncogenic pathways, including Ras/mitogen-activated protein kinase, Notch, phosphoinositide 3-kinase (PI3K)/AKT, Hippo, and mammalian target of rapamycin (mTOR). […] Recent genomic studies of meningiomas have elucidated a rich array of recurrent non NF2 mutations, typically in TNF receptor-associated factor 7 (TRAF7), Kruppel-like factor 4 (KLF4), v-Akt murine thymoma viral oncogene homolog 1 (AKT1), RNA polymerase II subunit A (POLR2A), Telomerase reverse transcriptase (TERT), smoothened/frizzled class receptor (SMO), and Phosphadidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). Non-NF2 mutations are frequently identified in grade I tumors and are genomically stable, with the absence of large-scale chromosomal amplifications or deletions.

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

  https://www.mdpi.com/2227-9059/9/3/319

  NF2 is the most common and well-known familial syndrome associated with meningioma risk. NF2 is caused by a germline mutation of the NF2 gene on chromosome 22q12 and is inherited in an autosomal dominant pattern. Over 50% of NF2 patients will develop at least one intracranial meningioma in their lifetime. […] In the 1990s, the NF2 gene was discovered to be a major driver of meningioma development. NF2 is a tumor suppressor gene located on chromosome 22q12 that encodes the Merlin protein. Merlin is a scaffold protein that belongs to the BAND 4.1 FERM gene family. Loss of NF2 can activate oncogenic pathways, including Ras/mitogen-activated protein kinase, Notch, phosphoinositide 3-kinase (PI3K)/AKT, Hippo, and mammalian target of rapamycin (mTOR). […] Recent genomic studies of meningiomas have elucidated a rich array of recurrent non NF2 mutations, typically in TNF receptor-associated factor 7 (TRAF7), Kruppel-like factor 4 (KLF4), v-Akt murine thymoma viral oncogene homolog 1 (AKT1), RNA polymerase II subunit A (POLR2A), Telomerase reverse transcriptase (TERT), smoothened/frizzled class receptor (SMO), and Phosphadidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). Non-NF2 mutations are frequently identified in grade I tumors and are genomically stable, with the absence of large-scale chromosomal amplifications or deletions.

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

  https://www.mdpi.com/2227-9059/9/3/319

  NF2 is the most common and well-known familial syndrome associated with meningioma risk. NF2 is caused by a germline mutation of the NF2 gene on chromosome 22q12 and is inherited in an autosomal dominant pattern. Over 50% of NF2 patients will develop at least one intracranial meningioma in their lifetime. […] In the 1990s, the NF2 gene was discovered to be a major driver of meningioma development. NF2 is a tumor suppressor gene located on chromosome 22q12 that encodes the Merlin protein. Merlin is a scaffold protein that belongs to the BAND 4.1 FERM gene family. Loss of NF2 can activate oncogenic pathways, including Ras/mitogen-activated protein kinase, Notch, phosphoinositide 3-kinase (PI3K)/AKT, Hippo, and mammalian target of rapamycin (mTOR). […] Recent genomic studies of meningiomas have elucidated a rich array of recurrent non NF2 mutations, typically in TNF receptor-associated factor 7 (TRAF7), Kruppel-like factor 4 (KLF4), v-Akt murine thymoma viral oncogene homolog 1 (AKT1), RNA polymerase II subunit A (POLR2A), Telomerase reverse transcriptase (TERT), smoothened/frizzled class receptor (SMO), and Phosphadidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). Non-NF2 mutations are frequently identified in grade I tumors and are genomically stable, with the absence of large-scale chromosomal amplifications or deletions.

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

  https://www.mdpi.com/2227-9059/9/3/319

  NF2 is the most common and well-known familial syndrome associated with meningioma risk. NF2 is caused by a germline mutation of the NF2 gene on chromosome 22q12 and is inherited in an autosomal dominant pattern. Over 50% of NF2 patients will develop at least one intracranial meningioma in their lifetime. […] In the 1990s, the NF2 gene was discovered to be a major driver of meningioma development. NF2 is a tumor suppressor gene located on chromosome 22q12 that encodes the Merlin protein. Merlin is a scaffold protein that belongs to the BAND 4.1 FERM gene family. Loss of NF2 can activate oncogenic pathways, including Ras/mitogen-activated protein kinase, Notch, phosphoinositide 3-kinase (PI3K)/AKT, Hippo, and mammalian target of rapamycin (mTOR). […] Recent genomic studies of meningiomas have elucidated a rich array of recurrent non NF2 mutations, typically in TNF receptor-associated factor 7 (TRAF7), Kruppel-like factor 4 (KLF4), v-Akt murine thymoma viral oncogene homolog 1 (AKT1), RNA polymerase II subunit A (POLR2A), Telomerase reverse transcriptase (TERT), smoothened/frizzled class receptor (SMO), and Phosphadidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). Non-NF2 mutations are frequently identified in grade I tumors and are genomically stable, with the absence of large-scale chromosomal amplifications or deletions.

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

  https://www.mdpi.com/2227-9059/9/3/319

  NF2 is the most common and well-known familial syndrome associated with meningioma risk. NF2 is caused by a germline mutation of the NF2 gene on chromosome 22q12 and is inherited in an autosomal dominant pattern. Over 50% of NF2 patients will develop at least one intracranial meningioma in their lifetime. […] In the 1990s, the NF2 gene was discovered to be a major driver of meningioma development. NF2 is a tumor suppressor gene located on chromosome 22q12 that encodes the Merlin protein. Merlin is a scaffold protein that belongs to the BAND 4.1 FERM gene family. Loss of NF2 can activate oncogenic pathways, including Ras/mitogen-activated protein kinase, Notch, phosphoinositide 3-kinase (PI3K)/AKT, Hippo, and mammalian target of rapamycin (mTOR). […] Recent genomic studies of meningiomas have elucidated a rich array of recurrent non NF2 mutations, typically in TNF receptor-associated factor 7 (TRAF7), Kruppel-like factor 4 (KLF4), v-Akt murine thymoma viral oncogene homolog 1 (AKT1), RNA polymerase II subunit A (POLR2A), Telomerase reverse transcriptase (TERT), smoothened/frizzled class receptor (SMO), and Phosphadidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). Non-NF2 mutations are frequently identified in grade I tumors and are genomically stable, with the absence of large-scale chromosomal amplifications or deletions.

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

  https://www.mdpi.com/2227-9059/9/3/319

  NF2 is the most common and well-known familial syndrome associated with meningioma risk. NF2 is caused by a germline mutation of the NF2 gene on chromosome 22q12 and is inherited in an autosomal dominant pattern. Over 50% of NF2 patients will develop at least one intracranial meningioma in their lifetime. […] In the 1990s, the NF2 gene was discovered to be a major driver of meningioma development. NF2 is a tumor suppressor gene located on chromosome 22q12 that encodes the Merlin protein. Merlin is a scaffold protein that belongs to the BAND 4.1 FERM gene family. Loss of NF2 can activate oncogenic pathways, including Ras/mitogen-activated protein kinase, Notch, phosphoinositide 3-kinase (PI3K)/AKT, Hippo, and mammalian target of rapamycin (mTOR). […] Recent genomic studies of meningiomas have elucidated a rich array of recurrent non NF2 mutations, typically in TNF receptor-associated factor 7 (TRAF7), Kruppel-like factor 4 (KLF4), v-Akt murine thymoma viral oncogene homolog 1 (AKT1), RNA polymerase II subunit A (POLR2A), Telomerase reverse transcriptase (TERT), smoothened/frizzled class receptor (SMO), and Phosphadidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). Non-NF2 mutations are frequently identified in grade I tumors and are genomically stable, with the absence of large-scale chromosomal amplifications or deletions.

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

  https://www.mdpi.com/2227-9059/9/3/319

  NF2 is the most common and well-known familial syndrome associated with meningioma risk. NF2 is caused by a germline mutation of the NF2 gene on chromosome 22q12 and is inherited in an autosomal dominant pattern. Over 50% of NF2 patients will develop at least one intracranial meningioma in their lifetime. […] In the 1990s, the NF2 gene was discovered to be a major driver of meningioma development. NF2 is a tumor suppressor gene located on chromosome 22q12 that encodes the Merlin protein. Merlin is a scaffold protein that belongs to the BAND 4.1 FERM gene family. Loss of NF2 can activate oncogenic pathways, including Ras/mitogen-activated protein kinase, Notch, phosphoinositide 3-kinase (PI3K)/AKT, Hippo, and mammalian target of rapamycin (mTOR). […] Recent genomic studies of meningiomas have elucidated a rich array of recurrent non NF2 mutations, typically in TNF receptor-associated factor 7 (TRAF7), Kruppel-like factor 4 (KLF4), v-Akt murine thymoma viral oncogene homolog 1 (AKT1), RNA polymerase II subunit A (POLR2A), Telomerase reverse transcriptase (TERT), smoothened/frizzled class receptor (SMO), and Phosphadidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). Non-NF2 mutations are frequently identified in grade I tumors and are genomically stable, with the absence of large-scale chromosomal amplifications or deletions.

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

  https://www.mdpi.com/2227-9059/9/3/319

  NF2 is the most common and well-known familial syndrome associated with meningioma risk. NF2 is caused by a germline mutation of the NF2 gene on chromosome 22q12 and is inherited in an autosomal dominant pattern. Over 50% of NF2 patients will develop at least one intracranial meningioma in their lifetime. […] In the 1990s, the NF2 gene was discovered to be a major driver of meningioma development. NF2 is a tumor suppressor gene located on chromosome 22q12 that encodes the Merlin protein. Merlin is a scaffold protein that belongs to the BAND 4.1 FERM gene family. Loss of NF2 can activate oncogenic pathways, including Ras/mitogen-activated protein kinase, Notch, phosphoinositide 3-kinase (PI3K)/AKT, Hippo, and mammalian target of rapamycin (mTOR). […] Recent genomic studies of meningiomas have elucidated a rich array of recurrent non NF2 mutations, typically in TNF receptor-associated factor 7 (TRAF7), Kruppel-like factor 4 (KLF4), v-Akt murine thymoma viral oncogene homolog 1 (AKT1), RNA polymerase II subunit A (POLR2A), Telomerase reverse transcriptase (TERT), smoothened/frizzled class receptor (SMO), and Phosphadidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). Non-NF2 mutations are frequently identified in grade I tumors and are genomically stable, with the absence of large-scale chromosomal amplifications or deletions.

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

  https://www.mdpi.com/2227-9059/9/3/319

  NF2 is the most common and well-known familial syndrome associated with meningioma risk. NF2 is caused by a germline mutation of the NF2 gene on chromosome 22q12 and is inherited in an autosomal dominant pattern. Over 50% of NF2 patients will develop at least one intracranial meningioma in their lifetime. […] In the 1990s, the NF2 gene was discovered to be a major driver of meningioma development. NF2 is a tumor suppressor gene located on chromosome 22q12 that encodes the Merlin protein. Merlin is a scaffold protein that belongs to the BAND 4.1 FERM gene family. Loss of NF2 can activate oncogenic pathways, including Ras/mitogen-activated protein kinase, Notch, phosphoinositide 3-kinase (PI3K)/AKT, Hippo, and mammalian target of rapamycin (mTOR). […] Recent genomic studies of meningiomas have elucidated a rich array of recurrent non NF2 mutations, typically in TNF receptor-associated factor 7 (TRAF7), Kruppel-like factor 4 (KLF4), v-Akt murine thymoma viral oncogene homolog 1 (AKT1), RNA polymerase II subunit A (POLR2A), Telomerase reverse transcriptase (TERT), smoothened/frizzled class receptor (SMO), and Phosphadidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). Non-NF2 mutations are frequently identified in grade I tumors and are genomically stable, with the absence of large-scale chromosomal amplifications or deletions.

• #31 Molecular Mechanism and Approach in Progression of Meningioma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7518150/

  The genetic changes of meningioma is associated with the poor prognosis. A study have shown that activating mutations in the promoter of the telomerase reverse transcriptase (TERT) gene promote the aggressiveness of meningiomas and reduce the survival of patients. […] The growth and proliferation of tumor cells are closely related to cell cycle dysregulation. For example, abnormal expression of cyclin, cyclin dependent kinases or their inhibitors often leads to enhanced proliferation and differentiation of meningioma cells. […] The adhesiveness of malignant cells is usually lower than that of normal cells. It was found that various cell adhesion molecules are expressed abnormally during the malignant invasion of meningioma. […] Meningioma is a vascular-rich type of tumor, especially atypical and anaplastic meningioma, which are likely to relapse, suggesting that angiogenesis plays an important role in its malignant-type behavior. […] Inhibition of apoptosis is closely associated with the occurrence, development and prognosis of tumors in meningioma. Several studies have found that the Wnt signaling pathway plays an important role in the development of meningioma, which is involved in apoptosis.

• #32 Pathology Outlines – Meningioma

  https://www.pathologyoutlines.com/topic/cnstumormeningiomageneral.html

  Non-NF2 meningiomas are enriched in mutations in TRAF2, KLF4, AKT1 and SMO, most of which are benign and preferentially located in the skull base (Science 2013;339:1077) […] Nearly 100% of secretory meningioma contain TRAF7 / KLF4 comutations, mutually exclusive to NF2 (Science 2013;339:1077) […] Angiomatous meningiomas contain multiple chromosome alterations, particularly gains of 5 and 20 (100% and 89%); blood vessels are nonneoplastic in origin (Oncotarget 2014;5:10596) […] DNA methylation profiling of meningioma distinguished 6 methylation classes (MCs) in adults, benign (ben) 1 – 3, intermediate (int) A and B and malignant (mal) […] DNA methylation based meningioma classification is reported to better predict tumor recurrence and prognosis than the WHO histological classification (Lancet Oncol 2017;18:682)

• #33 Pathology Outlines – Meningioma

  https://www.pathologyoutlines.com/topic/cnstumormeningiomageneral.html

  Non-NF2 meningiomas are enriched in mutations in TRAF2, KLF4, AKT1 and SMO, most of which are benign and preferentially located in the skull base (Science 2013;339:1077) […] Nearly 100% of secretory meningioma contain TRAF7 / KLF4 comutations, mutually exclusive to NF2 (Science 2013;339:1077) […] Angiomatous meningiomas contain multiple chromosome alterations, particularly gains of 5 and 20 (100% and 89%); blood vessels are nonneoplastic in origin (Oncotarget 2014;5:10596) […] DNA methylation profiling of meningioma distinguished 6 methylation classes (MCs) in adults, benign (ben) 1 – 3, intermediate (int) A and B and malignant (mal) […] DNA methylation based meningioma classification is reported to better predict tumor recurrence and prognosis than the WHO histological classification (Lancet Oncol 2017;18:682)

• #34 The molecular genetics and tumor pathogenesis of meningiomas and the future directions of meningioma treatments in: Neurosurgical Focus Volume 30 Issue 5 (2011) Journals

  https://thejns.org/focus/view/journals/neurosurg-focus/30/5/2011.2.focus1116.xml

  Studies have also implicated a myriad of aberrant signaling pathways involved with meningioma tumorigenesis, including those involved with proliferation, angiogenesis, and autocrine loops. Understanding these disrupted pathways will aid in deciphering the relationship between various genetic changes and their downstream effects on meningioma pathogenesis. […] Despite advancements in our understanding of meningioma pathogenesis, the conventional treatments, including surgery, radiotherapy, and stereotactic radiosurgery, have remained largely stagnant. Surgery and radiation therapy are curative in the majority of lesions, yet treatment remains challenging for meningiomas that are recurrent, aggressive, or refractory to conventional treatments. Future therapies will include combinations of targeted molecular agents as a result of continued progress in the understanding of genetic and biological changes associated with meningiomas.

• #35 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  The RB/p53 pathways and its impact on cell cycle dysregulation. […] RB has a central role in the inhibition of cell cycle progression at the G1/S-phase checkpoint. […] Briefly, RB binds (and inhibits) to the E2F transcription factor. […] Once cyclin D expression is upregulated (e.g. under mitogenic stimuli) it binds to either Cdk4 or Cdk6, and phosphorylates RB; RB phosphorylation induces release of the active E2F factor, leading to the transcription of genes which are critical for the transition from the G1 to the S-phase. […] p16INK4a and p15INK4b prevent S-phase entry by inhibiting the Cdk4/cyclin D complex. […] In turn, the p53 pathway acts as a feedback inhibitor of the RB pathway, by inducing cell cycle arrest, DNA repair and apoptosis in case of aberrant RB pathway activation.

• #36 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  The RB/p53 pathways and its impact on cell cycle dysregulation. […] RB has a central role in the inhibition of cell cycle progression at the G1/S-phase checkpoint. […] Briefly, RB binds (and inhibits) to the E2F transcription factor. […] Once cyclin D expression is upregulated (e.g. under mitogenic stimuli) it binds to either Cdk4 or Cdk6, and phosphorylates RB; RB phosphorylation induces release of the active E2F factor, leading to the transcription of genes which are critical for the transition from the G1 to the S-phase. […] p16INK4a and p15INK4b prevent S-phase entry by inhibiting the Cdk4/cyclin D complex. […] In turn, the p53 pathway acts as a feedback inhibitor of the RB pathway, by inducing cell cycle arrest, DNA repair and apoptosis in case of aberrant RB pathway activation.

• #37 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  Dysregulation of these two pathways in higher-grade meningiomas is frequently associated with loss of p16INK4a, p15INK4b and p14ARF, increased cell proliferation and tumor progression. […] In addition, accumulating evidences indicate that hypermethylation- associated loss of function of RB, overexpression of the MDM2 gene/protein and loss of expression of MEG3 (an anti-proliferative tumor suppressor that induces activation of p53 by a transcriptional effect) in higher grade meningiomas, might further contribute to dysregulation of both cell cycle-associated pathways during meningioma progression. […] Multiple studies have demonstrated enhanced expression of several growth factors, and activation of autocrine loops, which act as extra- and intracellular signals that induce tumor growth, cell migration, and angiogenesis, mostly via the MAPK and PI3K/Akt signaling pathways.

• #38 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  Dysregulation of these two pathways in higher-grade meningiomas is frequently associated with loss of p16INK4a, p15INK4b and p14ARF, increased cell proliferation and tumor progression. […] In addition, accumulating evidences indicate that hypermethylation- associated loss of function of RB, overexpression of the MDM2 gene/protein and loss of expression of MEG3 (an anti-proliferative tumor suppressor that induces activation of p53 by a transcriptional effect) in higher grade meningiomas, might further contribute to dysregulation of both cell cycle-associated pathways during meningioma progression. […] Multiple studies have demonstrated enhanced expression of several growth factors, and activation of autocrine loops, which act as extra- and intracellular signals that induce tumor growth, cell migration, and angiogenesis, mostly via the MAPK and PI3K/Akt signaling pathways.

• #39 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  Dysregulation of these two pathways in higher-grade meningiomas is frequently associated with loss of p16INK4a, p15INK4b and p14ARF, increased cell proliferation and tumor progression. […] In addition, accumulating evidences indicate that hypermethylation- associated loss of function of RB, overexpression of the MDM2 gene/protein and loss of expression of MEG3 (an anti-proliferative tumor suppressor that induces activation of p53 by a transcriptional effect) in higher grade meningiomas, might further contribute to dysregulation of both cell cycle-associated pathways during meningioma progression. […] Multiple studies have demonstrated enhanced expression of several growth factors, and activation of autocrine loops, which act as extra- and intracellular signals that induce tumor growth, cell migration, and angiogenesis, mostly via the MAPK and PI3K/Akt signaling pathways.

• #40 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  Among others, the platelet-derived growth factor BB (PDGF-BB) and its PDGFR- receptor have been found to be frequently overexpressed in meningiomas (typically at greater levels in high vs. low grade tumors), leading to meningioma cell proliferation via an autocrine and/or paracrine loop. […] Similarly, the epidermal growth factor receptor (EGFR), and both their EGF and transforming growth factor-alpha (TGF) ligands, as well as some members of the insulin-like growth factor (IGF) system (e.g. IGF2) have all been associated with meningioma cell proliferation and tumor progression. […] Interestingly, Lallemand et al. reported that merlin regulates cell contact-mediated inhibition of proliferation by limiting the delivery of several growth factor receptors (e.g. ErbB2, ErbB3, IGF1R and PDGFR) at the plasma membrane of primary Schwann cells, and thereby inhibit the activity of the downstream mitogenic signaling pathways.

• #41 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  Among others, the platelet-derived growth factor BB (PDGF-BB) and its PDGFR- receptor have been found to be frequently overexpressed in meningiomas (typically at greater levels in high vs. low grade tumors), leading to meningioma cell proliferation via an autocrine and/or paracrine loop. […] Similarly, the epidermal growth factor receptor (EGFR), and both their EGF and transforming growth factor-alpha (TGF) ligands, as well as some members of the insulin-like growth factor (IGF) system (e.g. IGF2) have all been associated with meningioma cell proliferation and tumor progression. […] Interestingly, Lallemand et al. reported that merlin regulates cell contact-mediated inhibition of proliferation by limiting the delivery of several growth factor receptors (e.g. ErbB2, ErbB3, IGF1R and PDGFR) at the plasma membrane of primary Schwann cells, and thereby inhibit the activity of the downstream mitogenic signaling pathways.

• #42 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  VEGFA and its VEGFR-1 receptor have been associated with regulation of the development of new blood vessels and peritumoral edema in brain tumors, a common feature in meningioma patients. […] Of note, meningiomas express both VEGF and VEGFR, and VEGF expression correlates with the severity of peritumoral edema and tumor vascularization. […] Despite this, the precise mechanisms that regulate VEGF expression in meningiomas remain unknown. […] In human cells, VEGF is mainly regulated by the hypoxia inducible factor-1 (HIF-1) transcription factor and in meningiomas, HIF-1 expression correlates with VEGF expression and the degree of peritumoral edema. […] In addition, upregulation of VEGF expression can also be induced by other growth factors such as EGF and PDGF, suggesting that both growth factors and hypoxia stimulation may all contribute to control VEGF expression in these tumors.

• #43 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  VEGFA and its VEGFR-1 receptor have been associated with regulation of the development of new blood vessels and peritumoral edema in brain tumors, a common feature in meningioma patients. […] Of note, meningiomas express both VEGF and VEGFR, and VEGF expression correlates with the severity of peritumoral edema and tumor vascularization. […] Despite this, the precise mechanisms that regulate VEGF expression in meningiomas remain unknown. […] In human cells, VEGF is mainly regulated by the hypoxia inducible factor-1 (HIF-1) transcription factor and in meningiomas, HIF-1 expression correlates with VEGF expression and the degree of peritumoral edema. […] In addition, upregulation of VEGF expression can also be induced by other growth factors such as EGF and PDGF, suggesting that both growth factors and hypoxia stimulation may all contribute to control VEGF expression in these tumors.

• #44 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  VEGFA and its VEGFR-1 receptor have been associated with regulation of the development of new blood vessels and peritumoral edema in brain tumors, a common feature in meningioma patients. […] Of note, meningiomas express both VEGF and VEGFR, and VEGF expression correlates with the severity of peritumoral edema and tumor vascularization. […] Despite this, the precise mechanisms that regulate VEGF expression in meningiomas remain unknown. […] In human cells, VEGF is mainly regulated by the hypoxia inducible factor-1 (HIF-1) transcription factor and in meningiomas, HIF-1 expression correlates with VEGF expression and the degree of peritumoral edema. […] In addition, upregulation of VEGF expression can also be induced by other growth factors such as EGF and PDGF, suggesting that both growth factors and hypoxia stimulation may all contribute to control VEGF expression in these tumors.

• #45 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  Other growth factors that have been associated with the pathogenesis of meningiomas include: 1) the stromal cell-derived factor 1 (SDF1) CXC chemokine and its CXCR4 receptor, which might exert its mitogenic effects through the MAPK pathway; 2) the bone morphogenic proteins (BMPs) and their receptors (BMPR), which are associated with Smad 1 signaling, and; 3) the fibroblast growth factor (FGF) and its FGFR3 receptor, which are activated by the PI3K/Akt pathway. […] In contrast, TGF- and its receptors (TGF-RI and TGF-RII) may act as potential inhibitors of meningioma growth/proliferation through the Smad 2/3 apoptotic pathway, although the role of TGF- in meningioma tumorigenesis remains to be fully established. […] The mitogen-activated protein kinase (MAPK) pathway and the phosphatidylinositol 3-kinase (PI3K)/Akt pathway are both involved in multiple cellular processes (e.g. differentiation, growth, and apoptosis) associated with the pathogenesis of meningiomas, particularly with those tumors showing deregulated cell proliferation.

• #46 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  MAPKs are intracellular serine/threonine-specific protein kinases which are activated by extracellular stimuli (e.g., mitogen signals), leading to sequential activation of a kinase cascade triggered by the Ras/Raf-1/MEK-1/MAPK/ERK pathway and that ultimately, leads to phosphorylation/activation of transcription factors in the nucleus. […] PI3Ks are a family of intracellular signal transducer enzymes that phosphorylate inositol phospholipids. […] Activation of PI3K results in phosphorylation/activation of PKB/Akt and subsequently p70S6K, which are key elements of the cell growth-promoting effects of this pathway; alternatively, activating mutations of AKT have also been recently reported in a subset of meningiomas. […] In line with this, Johnson et al. found evidences for the activation of both the MAPK and the Akt/PKB pathways in meningiomas, upon growth factor receptor signaling via e.g. PDGF-BB and PDGF; furthermore, these authors showed that administration of MAPK or PI3K inhibitors induces progressive growth inhibition of meningioma cells in association with reduced phosphorylation of MAPK or Akt and p70S6K, respectively.

• #47 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  MAPKs are intracellular serine/threonine-specific protein kinases which are activated by extracellular stimuli (e.g., mitogen signals), leading to sequential activation of a kinase cascade triggered by the Ras/Raf-1/MEK-1/MAPK/ERK pathway and that ultimately, leads to phosphorylation/activation of transcription factors in the nucleus. […] PI3Ks are a family of intracellular signal transducer enzymes that phosphorylate inositol phospholipids. […] Activation of PI3K results in phosphorylation/activation of PKB/Akt and subsequently p70S6K, which are key elements of the cell growth-promoting effects of this pathway; alternatively, activating mutations of AKT have also been recently reported in a subset of meningiomas. […] In line with this, Johnson et al. found evidences for the activation of both the MAPK and the Akt/PKB pathways in meningiomas, upon growth factor receptor signaling via e.g. PDGF-BB and PDGF; furthermore, these authors showed that administration of MAPK or PI3K inhibitors induces progressive growth inhibition of meningioma cells in association with reduced phosphorylation of MAPK or Akt and p70S6K, respectively.

• #48 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  MAPKs are intracellular serine/threonine-specific protein kinases which are activated by extracellular stimuli (e.g., mitogen signals), leading to sequential activation of a kinase cascade triggered by the Ras/Raf-1/MEK-1/MAPK/ERK pathway and that ultimately, leads to phosphorylation/activation of transcription factors in the nucleus. […] PI3Ks are a family of intracellular signal transducer enzymes that phosphorylate inositol phospholipids. […] Activation of PI3K results in phosphorylation/activation of PKB/Akt and subsequently p70S6K, which are key elements of the cell growth-promoting effects of this pathway; alternatively, activating mutations of AKT have also been recently reported in a subset of meningiomas. […] In line with this, Johnson et al. found evidences for the activation of both the MAPK and the Akt/PKB pathways in meningiomas, upon growth factor receptor signaling via e.g. PDGF-BB and PDGF; furthermore, these authors showed that administration of MAPK or PI3K inhibitors induces progressive growth inhibition of meningioma cells in association with reduced phosphorylation of MAPK or Akt and p70S6K, respectively.

• #49 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  Moreover, COX-2 expression has been correlated with a greater degree of invasiveness to the brain or the adjacent soft tissues, tumor recurrence, a higher MIB-1 labeling index and VEGF levels, suggesting it may play an important role in the development and growth of meningiomas. […] Recent studies have found the mammalian target of rapamycin (mTOR) to be also involved in the signaling pathways associated with meningioma tumorigenesis. […] mTOR is a protein kinase that may be expressed in two distinct complexes (mTORC1 and mTORC2). […] mTORC1 regulates cell growth by promoting increased translation and protein synthesis through phosphorylation of the p70S6K and 4EBP1 (eukaryotic translation initiation factor 4E-binding protein 1) effector proteins; in turn, mTORC2 directly phosphorylates Akt, a step required for its full activation.

• #50 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  Recently, merlin has been identified as a negative regulator of mTORC1 and, James et al. have demonstrated that mTORC1 levels are elevated in tumors derived from patients with NF2 disease and in fibroblasts from an NF2-deficient mouse model. […] Thus, activation of mTORC1 has been associated with meningioma growth, and mTORC1 inhibitors have been shown to suppress meningioma growth in mouse models. […] However, the exact mechanism through which merlin inhibits mTORC1 still remains unclear. […] In contrast to its effects on mTORC1, merlin positively regulates the kinase activity of mTORC2, downstream phosphorylation of mTORC2 substrates, including Akt, being reduced upon acute merlin deficiency in cells. […] Nevertheless, the attenuated mTORC2 signaling profiles reported in response to the loss of merlin, could not be detected in NF2-deficient meningiomas.

• #51 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  The wingless (wnt)/-catenin pathway has also been implicated in meningioma progression, through an altered expression of several of its genes. […] Thus, early studies based on microarray gene expression profiling identified increased expression of genes such as CTNNB1, CDK5R1, ENC1 and CCND1. […] Subsequently, Pecina-Slaus et al. reported LOH of the E-cadherin (CDH1) and the adenomatous polyposis coli (APC) tumor suppressor genes in about one-third and half of the cases, respectively. […] Downregulation of E-cadherin expression in clinically aggressive and invasive meningiomas had already been described in association with upregulation and nuclear/perinuclear localization of -catenin, suggesting an important role for the WNT/ catenin pathway in meningioma tumorigenesis. […] Interestingly, Zhou et al. suggested a model in which active merlin would inhibit Wnt/-catenin signaling and maintain -catenin and N-cadherin complexed at the plasma membrane; loss of merlin would then lead to loss of contact inhibition and activation of Wnt/-catenin signaling, translocation of -catenin to the nucleus and expression of intracellular growth-associated proteins such as c-myc and cyclin D1.

• #52 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  The wingless (wnt)/-catenin pathway has also been implicated in meningioma progression, through an altered expression of several of its genes. […] Thus, early studies based on microarray gene expression profiling identified increased expression of genes such as CTNNB1, CDK5R1, ENC1 and CCND1. […] Subsequently, Pecina-Slaus et al. reported LOH of the E-cadherin (CDH1) and the adenomatous polyposis coli (APC) tumor suppressor genes in about one-third and half of the cases, respectively. […] Downregulation of E-cadherin expression in clinically aggressive and invasive meningiomas had already been described in association with upregulation and nuclear/perinuclear localization of -catenin, suggesting an important role for the WNT/ catenin pathway in meningioma tumorigenesis. […] Interestingly, Zhou et al. suggested a model in which active merlin would inhibit Wnt/-catenin signaling and maintain -catenin and N-cadherin complexed at the plasma membrane; loss of merlin would then lead to loss of contact inhibition and activation of Wnt/-catenin signaling, translocation of -catenin to the nucleus and expression of intracellular growth-associated proteins such as c-myc and cyclin D1.

• #53 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  The wingless (wnt)/-catenin pathway has also been implicated in meningioma progression, through an altered expression of several of its genes. […] Thus, early studies based on microarray gene expression profiling identified increased expression of genes such as CTNNB1, CDK5R1, ENC1 and CCND1. […] Subsequently, Pecina-Slaus et al. reported LOH of the E-cadherin (CDH1) and the adenomatous polyposis coli (APC) tumor suppressor genes in about one-third and half of the cases, respectively. […] Downregulation of E-cadherin expression in clinically aggressive and invasive meningiomas had already been described in association with upregulation and nuclear/perinuclear localization of -catenin, suggesting an important role for the WNT/ catenin pathway in meningioma tumorigenesis. […] Interestingly, Zhou et al. suggested a model in which active merlin would inhibit Wnt/-catenin signaling and maintain -catenin and N-cadherin complexed at the plasma membrane; loss of merlin would then lead to loss of contact inhibition and activation of Wnt/-catenin signaling, translocation of -catenin to the nucleus and expression of intracellular growth-associated proteins such as c-myc and cyclin D1.

• #54 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  The wingless (wnt)/-catenin pathway has also been implicated in meningioma progression, through an altered expression of several of its genes. […] Thus, early studies based on microarray gene expression profiling identified increased expression of genes such as CTNNB1, CDK5R1, ENC1 and CCND1. […] Subsequently, Pecina-Slaus et al. reported LOH of the E-cadherin (CDH1) and the adenomatous polyposis coli (APC) tumor suppressor genes in about one-third and half of the cases, respectively. […] Downregulation of E-cadherin expression in clinically aggressive and invasive meningiomas had already been described in association with upregulation and nuclear/perinuclear localization of -catenin, suggesting an important role for the WNT/ catenin pathway in meningioma tumorigenesis. […] Interestingly, Zhou et al. suggested a model in which active merlin would inhibit Wnt/-catenin signaling and maintain -catenin and N-cadherin complexed at the plasma membrane; loss of merlin would then lead to loss of contact inhibition and activation of Wnt/-catenin signaling, translocation of -catenin to the nucleus and expression of intracellular growth-associated proteins such as c-myc and cyclin D1.

• #55 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  The notch signaling pathway is involved in extracellular-to-intracellular signaling via the notch1-4 transmembrane proteins. […] Ligand proteins bind to the extracellular portion of the Notch proteins, resulting in proteolytic cleavage and release of the intracellular portion, which is translocated to the nucleus and initiates expression of the hairy/enhancer of split (HES) family of transcriptional regulators. […] Cuevas et al. comparatively analyzed the GEP of normal/reactive meninges and meningiomas of all histopathological grades, and demonstrated the potential involvement of the notch signaling pathway in meningiomas. […] Thus, HES1 expression was increased in all meningioma grades and it correlated with increased expression of notch1, notch2, and the jagged ligand; in contrast, transducin-like enhancer of split (TLE) 2 and TLE3, two co-repressors that modulate HES1 activity, were specifically upregulated in malignant meningiomas.

• #56 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  The notch signaling pathway is involved in extracellular-to-intracellular signaling via the notch1-4 transmembrane proteins. […] Ligand proteins bind to the extracellular portion of the Notch proteins, resulting in proteolytic cleavage and release of the intracellular portion, which is translocated to the nucleus and initiates expression of the hairy/enhancer of split (HES) family of transcriptional regulators. […] Cuevas et al. comparatively analyzed the GEP of normal/reactive meninges and meningiomas of all histopathological grades, and demonstrated the potential involvement of the notch signaling pathway in meningiomas. […] Thus, HES1 expression was increased in all meningioma grades and it correlated with increased expression of notch1, notch2, and the jagged ligand; in contrast, transducin-like enhancer of split (TLE) 2 and TLE3, two co-repressors that modulate HES1 activity, were specifically upregulated in malignant meningiomas.

• #57 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  The notch signaling pathway is involved in extracellular-to-intracellular signaling via the notch1-4 transmembrane proteins. […] Ligand proteins bind to the extracellular portion of the Notch proteins, resulting in proteolytic cleavage and release of the intracellular portion, which is translocated to the nucleus and initiates expression of the hairy/enhancer of split (HES) family of transcriptional regulators. […] Cuevas et al. comparatively analyzed the GEP of normal/reactive meninges and meningiomas of all histopathological grades, and demonstrated the potential involvement of the notch signaling pathway in meningiomas. […] Thus, HES1 expression was increased in all meningioma grades and it correlated with increased expression of notch1, notch2, and the jagged ligand; in contrast, transducin-like enhancer of split (TLE) 2 and TLE3, two co-repressors that modulate HES1 activity, were specifically upregulated in malignant meningiomas.

• #58 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  The notch signaling pathway is involved in extracellular-to-intracellular signaling via the notch1-4 transmembrane proteins. […] Ligand proteins bind to the extracellular portion of the Notch proteins, resulting in proteolytic cleavage and release of the intracellular portion, which is translocated to the nucleus and initiates expression of the hairy/enhancer of split (HES) family of transcriptional regulators. […] Cuevas et al. comparatively analyzed the GEP of normal/reactive meninges and meningiomas of all histopathological grades, and demonstrated the potential involvement of the notch signaling pathway in meningiomas. […] Thus, HES1 expression was increased in all meningioma grades and it correlated with increased expression of notch1, notch2, and the jagged ligand; in contrast, transducin-like enhancer of split (TLE) 2 and TLE3, two co-repressors that modulate HES1 activity, were specifically upregulated in malignant meningiomas.

• #59 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  Furthermore, deregulation of notch in meningiomas results in tetraploidy and chromosomal instability, further studies being required to elucidate the precise mechanism by which abnormal notch activation induces such genetic changes in meningiomas. […] When Hh binds its patched (PTCH) receptor, the smoothened (SMO) transmembrane protein is activated and initiates a signaling cascade that results in the activation of the GLI transcription factors (e.g. GLI1 and GLI2) and subsequent transcription of genes involved in cell growth, proliferation, angiogenesis, matrix remodeling, and stem cell homeostasis. […] Recently, Laurendeau et al. have analyzed the mRNA expression patterns of 32 Hh pathway-related genes in 36 meningiomas and found increased levels of 16 genes involved in the activation of the Hh pathway (e.g. SMO, GLI1, GLI2, GLIS2, FOXM1, IGF2 and SPP1) and cell growth, together with decreased expression of 7 genes involved in the inhibition of the Hh pathway (e.g. the PTCH1 tumor suppressor); some of these genes further showed different expression profiles among tumors of different histopathological grades, suggesting distinctly altered profiles early during tumorigenesis vs. progression to more aggressive tumor lesions.

• #60 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  Furthermore, deregulation of notch in meningiomas results in tetraploidy and chromosomal instability, further studies being required to elucidate the precise mechanism by which abnormal notch activation induces such genetic changes in meningiomas. […] When Hh binds its patched (PTCH) receptor, the smoothened (SMO) transmembrane protein is activated and initiates a signaling cascade that results in the activation of the GLI transcription factors (e.g. GLI1 and GLI2) and subsequent transcription of genes involved in cell growth, proliferation, angiogenesis, matrix remodeling, and stem cell homeostasis. […] Recently, Laurendeau et al. have analyzed the mRNA expression patterns of 32 Hh pathway-related genes in 36 meningiomas and found increased levels of 16 genes involved in the activation of the Hh pathway (e.g. SMO, GLI1, GLI2, GLIS2, FOXM1, IGF2 and SPP1) and cell growth, together with decreased expression of 7 genes involved in the inhibition of the Hh pathway (e.g. the PTCH1 tumor suppressor); some of these genes further showed different expression profiles among tumors of different histopathological grades, suggesting distinctly altered profiles early during tumorigenesis vs. progression to more aggressive tumor lesions.

• #61 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  Furthermore, deregulation of notch in meningiomas results in tetraploidy and chromosomal instability, further studies being required to elucidate the precise mechanism by which abnormal notch activation induces such genetic changes in meningiomas. […] When Hh binds its patched (PTCH) receptor, the smoothened (SMO) transmembrane protein is activated and initiates a signaling cascade that results in the activation of the GLI transcription factors (e.g. GLI1 and GLI2) and subsequent transcription of genes involved in cell growth, proliferation, angiogenesis, matrix remodeling, and stem cell homeostasis. […] Recently, Laurendeau et al. have analyzed the mRNA expression patterns of 32 Hh pathway-related genes in 36 meningiomas and found increased levels of 16 genes involved in the activation of the Hh pathway (e.g. SMO, GLI1, GLI2, GLIS2, FOXM1, IGF2 and SPP1) and cell growth, together with decreased expression of 7 genes involved in the inhibition of the Hh pathway (e.g. the PTCH1 tumor suppressor); some of these genes further showed different expression profiles among tumors of different histopathological grades, suggesting distinctly altered profiles early during tumorigenesis vs. progression to more aggressive tumor lesions.

• #62 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  Interestingly, recent reports have identified SMO mutations in meningiomas lacking NF2 mutations, which further supports the potentially relevant role of this pathway in the development of at least some meningiomas. […] Based on all what has been described above, at present it is well-established that meningiomas are cytogenetically heterogenous tumors. […] Consequently, for decades now, attempts have been made to classify meningiomas on cytogenetic grounds. […] The first cytogenetic classifications and cytogenetic models of progression of meningiomas were proposed in the 1990s. […] Weber et al. proposed a model of genomic alterations associated with meningioma progression based on comparative genomic hybridization (CGH) analysis of tumors of different grades. […] Later on, Ketter et al. and Zang et al., subdivided meningiomas into four subgroups based on their cytogenetic findings: Group 0, included meningiomas with a normal diploid chromosomal set; Group 1, consisted of tumors with monosomy 22 as the sole cytogenetic alteration; Group 2, was composed of tumors showing marked hypodiploidy with loss of additional autosomes, and finally; Group 3 included meningiomas with deletions of the short arm of chromosome 1, in association with other chromosomal aberrations such as loss of chromosome 22.

• #63 Molecular Mechanism and Approach in Progression of Meningioma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7518150/

  The genetic changes of meningioma is associated with the poor prognosis. A study have shown that activating mutations in the promoter of the telomerase reverse transcriptase (TERT) gene promote the aggressiveness of meningiomas and reduce the survival of patients. […] The growth and proliferation of tumor cells are closely related to cell cycle dysregulation. For example, abnormal expression of cyclin, cyclin dependent kinases or their inhibitors often leads to enhanced proliferation and differentiation of meningioma cells. […] The adhesiveness of malignant cells is usually lower than that of normal cells. It was found that various cell adhesion molecules are expressed abnormally during the malignant invasion of meningioma. […] Meningioma is a vascular-rich type of tumor, especially atypical and anaplastic meningioma, which are likely to relapse, suggesting that angiogenesis plays an important role in its malignant-type behavior. […] Inhibition of apoptosis is closely associated with the occurrence, development and prognosis of tumors in meningioma. Several studies have found that the Wnt signaling pathway plays an important role in the development of meningioma, which is involved in apoptosis.

• #64 Molecular Mechanism and Approach in Progression of Meningioma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7518150/

  The genetic changes of meningioma is associated with the poor prognosis. A study have shown that activating mutations in the promoter of the telomerase reverse transcriptase (TERT) gene promote the aggressiveness of meningiomas and reduce the survival of patients. […] The growth and proliferation of tumor cells are closely related to cell cycle dysregulation. For example, abnormal expression of cyclin, cyclin dependent kinases or their inhibitors often leads to enhanced proliferation and differentiation of meningioma cells. […] The adhesiveness of malignant cells is usually lower than that of normal cells. It was found that various cell adhesion molecules are expressed abnormally during the malignant invasion of meningioma. […] Meningioma is a vascular-rich type of tumor, especially atypical and anaplastic meningioma, which are likely to relapse, suggesting that angiogenesis plays an important role in its malignant-type behavior. […] Inhibition of apoptosis is closely associated with the occurrence, development and prognosis of tumors in meningioma. Several studies have found that the Wnt signaling pathway plays an important role in the development of meningioma, which is involved in apoptosis.

• #65 Molecular Mechanism and Approach in Progression of Meningioma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7518150/

  The genetic changes of meningioma is associated with the poor prognosis. A study have shown that activating mutations in the promoter of the telomerase reverse transcriptase (TERT) gene promote the aggressiveness of meningiomas and reduce the survival of patients. […] The growth and proliferation of tumor cells are closely related to cell cycle dysregulation. For example, abnormal expression of cyclin, cyclin dependent kinases or their inhibitors often leads to enhanced proliferation and differentiation of meningioma cells. […] The adhesiveness of malignant cells is usually lower than that of normal cells. It was found that various cell adhesion molecules are expressed abnormally during the malignant invasion of meningioma. […] Meningioma is a vascular-rich type of tumor, especially atypical and anaplastic meningioma, which are likely to relapse, suggesting that angiogenesis plays an important role in its malignant-type behavior. […] Inhibition of apoptosis is closely associated with the occurrence, development and prognosis of tumors in meningioma. Several studies have found that the Wnt signaling pathway plays an important role in the development of meningioma, which is involved in apoptosis.

• #66 Molecular Mechanism and Approach in Progression of Meningioma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7518150/

  The genetic changes of meningioma is associated with the poor prognosis. A study have shown that activating mutations in the promoter of the telomerase reverse transcriptase (TERT) gene promote the aggressiveness of meningiomas and reduce the survival of patients. […] The growth and proliferation of tumor cells are closely related to cell cycle dysregulation. For example, abnormal expression of cyclin, cyclin dependent kinases or their inhibitors often leads to enhanced proliferation and differentiation of meningioma cells. […] The adhesiveness of malignant cells is usually lower than that of normal cells. It was found that various cell adhesion molecules are expressed abnormally during the malignant invasion of meningioma. […] Meningioma is a vascular-rich type of tumor, especially atypical and anaplastic meningioma, which are likely to relapse, suggesting that angiogenesis plays an important role in its malignant-type behavior. […] Inhibition of apoptosis is closely associated with the occurrence, development and prognosis of tumors in meningioma. Several studies have found that the Wnt signaling pathway plays an important role in the development of meningioma, which is involved in apoptosis.

• #67 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  The main characteristic of cells lacking the NF2 protein is the loss of contact-mediated inhibition of cell proliferation. […] Additionally, loss of merlin activity has been associated with increased levels of ErbB receptors in primary Schwann cells, which regulate downstream mitogenic signaling pathways (e.g. Ras/Raf/MEK/ERK and PI3K/AKT); altogether, these findings support a relevant role of merlin in tumorigenesis in meningiomas. […] In line with this hypothesis, mice which are heterozygous for NF2 mutations more frequently develop metastatic tumors, and both in vivo and in vitro re-expression of wild type merlin leads to reduced tumor growth and decreased cell motility. […] Since the merlin functions include linking membrane proteins to the cytoskeleton, it has been hypothesized that alterations in merlin may substantially affect cell shape and might favor the appearance of a more mesenchymal-like phenotype rather than the epithelioid one, which is more commonly observed in wild type NF2 meningiomas.

• #68 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  The main characteristic of cells lacking the NF2 protein is the loss of contact-mediated inhibition of cell proliferation. […] Additionally, loss of merlin activity has been associated with increased levels of ErbB receptors in primary Schwann cells, which regulate downstream mitogenic signaling pathways (e.g. Ras/Raf/MEK/ERK and PI3K/AKT); altogether, these findings support a relevant role of merlin in tumorigenesis in meningiomas. […] In line with this hypothesis, mice which are heterozygous for NF2 mutations more frequently develop metastatic tumors, and both in vivo and in vitro re-expression of wild type merlin leads to reduced tumor growth and decreased cell motility. […] Since the merlin functions include linking membrane proteins to the cytoskeleton, it has been hypothesized that alterations in merlin may substantially affect cell shape and might favor the appearance of a more mesenchymal-like phenotype rather than the epithelioid one, which is more commonly observed in wild type NF2 meningiomas.

• #69 Meningioma recurrence

  https://www.degruyter.com/document/doi/10.1515/med-2016-0032/html?lang=en

  Meningioma is also a component of numerous familiar tumour syndromes. […] A novel avenue to an understanding of meningioma pathogenesis is research into epigenetic mechanisms. […] Although NF2 is relatively frequently mutated in meningioma, epigenetic alteration of NF2 is rare. […] The third major epigenetic factor, micro RNAs (miRNAs), are important in regulating post-translational silencing. […] The clinical behaviour and risk of recurrence have a very close association with the histological grade of the tumour. […] Several studies have proven the close association between histological grade and risk of recurrence. […] The extent of resection is graded according to Simpson, using a 5-tier scale. […] There is close correlation between Simpson grade and risk of recurrence. […] In higher Simpson grades (III-V) disease-free survival is shorter, quality of life is reduced, and there is an increased chance of early recurrence of the tumour. […] Although meningiomas are tumours that occur with high frequency, the mechanisms underlying pathogenesis, recurrence, and progression remain poorly understood.

• #70 Pathology Outlines – Meningioma

  https://www.pathologyoutlines.com/topic/cnstumormeningiomageneral.html

  Non-NF2 meningiomas are enriched in mutations in TRAF2, KLF4, AKT1 and SMO, most of which are benign and preferentially located in the skull base (Science 2013;339:1077) […] Nearly 100% of secretory meningioma contain TRAF7 / KLF4 comutations, mutually exclusive to NF2 (Science 2013;339:1077) […] Angiomatous meningiomas contain multiple chromosome alterations, particularly gains of 5 and 20 (100% and 89%); blood vessels are nonneoplastic in origin (Oncotarget 2014;5:10596) […] DNA methylation profiling of meningioma distinguished 6 methylation classes (MCs) in adults, benign (ben) 1 – 3, intermediate (int) A and B and malignant (mal) […] DNA methylation based meningioma classification is reported to better predict tumor recurrence and prognosis than the WHO histological classification (Lancet Oncol 2017;18:682)

• #71 Pathology Outlines – Meningioma

  https://www.pathologyoutlines.com/topic/cnstumormeningiomageneral.html

  Non-NF2 meningiomas are enriched in mutations in TRAF2, KLF4, AKT1 and SMO, most of which are benign and preferentially located in the skull base (Science 2013;339:1077) […] Nearly 100% of secretory meningioma contain TRAF7 / KLF4 comutations, mutually exclusive to NF2 (Science 2013;339:1077) […] Angiomatous meningiomas contain multiple chromosome alterations, particularly gains of 5 and 20 (100% and 89%); blood vessels are nonneoplastic in origin (Oncotarget 2014;5:10596) […] DNA methylation profiling of meningioma distinguished 6 methylation classes (MCs) in adults, benign (ben) 1 – 3, intermediate (int) A and B and malignant (mal) […] DNA methylation based meningioma classification is reported to better predict tumor recurrence and prognosis than the WHO histological classification (Lancet Oncol 2017;18:682)

• #72 Meningioma Genomics: Gene Discovery, Molecular Mechanisms, And Clinical Correlations

  https://elischolar.library.yale.edu/ymtdl/3433/

  Meningiomas, the most common primary intracranial tumors, can cause significant morbidity and mortality, requiring novel targeted therapies. The genomic basis of approximately 80% of sporadic meningiomas has recently been established, however, the rest remain mutation-unknown. Identification of additional driver and/or co-driver genes could guide future targeted therapies. […] Recently established is the distinct subgroup of meningiomas harboring mutations in the SMARCB1 tumor suppressor gene, a core subunit of the SWI/SNF chromatin-remodeling complex. Notably, SWI/SNF mutations in other tumors have been associated with dysregulation of the PRC2 complex, an epigenetic regulator whose signature marker of activity is H3K27me3. However, the molecular mechanism of tumorigenesis in SWI/SNF-mutant meningiomas remains unknown, limiting options for targeted therapies.

• #73 Meningioma Genomics: Gene Discovery, Molecular Mechanisms, And Clinical Correlations

  https://elischolar.library.yale.edu/ymtdl/3433/

  Meningiomas, the most common primary intracranial tumors, can cause significant morbidity and mortality, requiring novel targeted therapies. The genomic basis of approximately 80% of sporadic meningiomas has recently been established, however, the rest remain mutation-unknown. Identification of additional driver and/or co-driver genes could guide future targeted therapies. […] Recently established is the distinct subgroup of meningiomas harboring mutations in the SMARCB1 tumor suppressor gene, a core subunit of the SWI/SNF chromatin-remodeling complex. Notably, SWI/SNF mutations in other tumors have been associated with dysregulation of the PRC2 complex, an epigenetic regulator whose signature marker of activity is H3K27me3. However, the molecular mechanism of tumorigenesis in SWI/SNF-mutant meningiomas remains unknown, limiting options for targeted therapies.

• #74 Meningioma Genomics: Gene Discovery, Molecular Mechanisms, And Clinical Correlations

  https://elischolar.library.yale.edu/ymtdl/3433/

  We demonstrate elevated H3K27me3 signal and concordantly decreased gene expression in SWI/SNF-mutant meningiomas, suggesting increased PRC2 activity either by decreased inhibition (loss-of-function) or potentiation (neomorphic function) by mutant SWI/SNF. Inhibitors of EZH2, the H3K27me3 catalytic subunit of PRC2, may thus prove efficacious in SWI/SNF-mutant meningiomas. […] In conclusion, this study identifies additional novel candidate meningioma driver mutations in SWI/SNF subunits, proposes a molecular mechanism underlying SWI/SNF-mutant meningiomas, and reveals novel genomic-clinical correlations in addition to validating previous associations. Overall, these results may guide future targeted therapies and clinical management to improve the outcomes of patients with meningiomas.

• #75 The role of m6A RNA methylation regulator in meningioma | Aging

  https://www.aging-us.com/article/205163/text

  Therefore, it was speculated that dysregulation of the m6A regulatory gene played a crucial role in the mechanism of meningiomas. […] We believed that IGFBP2 and METTL3 were survival-related m6A regulatory genes with critical prognostic value in meningiomas. […] The results of this study may provide a powerful reference for individualized treatment of meningiomas. […] The results of this study highlight the need for further verification and investigations on the complex biological mechanisms of these m6A targets in meningiomas. […] The high- and low-risk groups in the present study, based on methylation regulators, stimulated interest in meningioma pathogenesis. […] In general, the results suggested that the characteristic expression of m6A methylated genes is as a prognostic indicator of meningiomas. These m6A genes and their related pathways could serve as potential therapeutic targets for meningiomas. […] In conclusion, two m6A methylated genes (METTL3 and IGF2BP2) were identified and a RiskScore methylation regulatory network was constructed, which can be considered prognostic factors for meningioma.

• #76 The role of m6A RNA methylation regulator in meningioma | Aging

  https://www.aging-us.com/article/205163/text

  Therefore, it was speculated that dysregulation of the m6A regulatory gene played a crucial role in the mechanism of meningiomas. […] We believed that IGFBP2 and METTL3 were survival-related m6A regulatory genes with critical prognostic value in meningiomas. […] The results of this study may provide a powerful reference for individualized treatment of meningiomas. […] The results of this study highlight the need for further verification and investigations on the complex biological mechanisms of these m6A targets in meningiomas. […] The high- and low-risk groups in the present study, based on methylation regulators, stimulated interest in meningioma pathogenesis. […] In general, the results suggested that the characteristic expression of m6A methylated genes is as a prognostic indicator of meningiomas. These m6A genes and their related pathways could serve as potential therapeutic targets for meningiomas. […] In conclusion, two m6A methylated genes (METTL3 and IGF2BP2) were identified and a RiskScore methylation regulatory network was constructed, which can be considered prognostic factors for meningioma.

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

  https://www.mdpi.com/2227-9059/9/3/319

  Advances in molecular techniques over the last decade that include genomic and epigenomic data associated with meningiomas have been used to identify genetic biomarkers that may predict tumor behavior and prognosis. […] Chromosomal instability has repeatedly been shown to be one of the most frequent molecular alterations for tumor recurrence and prognosis. Accumulation of cytogenetic aberrations correlates with increasing tumor grades and aggressiveness, with higher-grade (atypical and anaplastic) meningiomas demonstrating an increasingly complex cytogenetic profile compared to benign meningiomas. […] While the majority of meningiomas occurs sporadically, there are many rare familial syndromes that increase the risk of developing these tumors. While exact molecular mechanisms have yet to be elucidated, these familial syndromes might provide insight behind sporadic meningioma tumorigenesis and implications for management.

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

  https://www.mdpi.com/2227-9059/9/3/319

  NF2 is the most common and well-known familial syndrome associated with meningioma risk. NF2 is caused by a germline mutation of the NF2 gene on chromosome 22q12 and is inherited in an autosomal dominant pattern. Over 50% of NF2 patients will develop at least one intracranial meningioma in their lifetime. […] In the 1990s, the NF2 gene was discovered to be a major driver of meningioma development. NF2 is a tumor suppressor gene located on chromosome 22q12 that encodes the Merlin protein. Merlin is a scaffold protein that belongs to the BAND 4.1 FERM gene family. Loss of NF2 can activate oncogenic pathways, including Ras/mitogen-activated protein kinase, Notch, phosphoinositide 3-kinase (PI3K)/AKT, Hippo, and mammalian target of rapamycin (mTOR). […] Recent genomic studies of meningiomas have elucidated a rich array of recurrent non NF2 mutations, typically in TNF receptor-associated factor 7 (TRAF7), Kruppel-like factor 4 (KLF4), v-Akt murine thymoma viral oncogene homolog 1 (AKT1), RNA polymerase II subunit A (POLR2A), Telomerase reverse transcriptase (TERT), smoothened/frizzled class receptor (SMO), and Phosphadidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). Non-NF2 mutations are frequently identified in grade I tumors and are genomically stable, with the absence of large-scale chromosomal amplifications or deletions.

• #79 Meningioma – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/meningioma/symptoms-causes/syc-20355643

  A meningioma is a tumor that grows from the membranes that surround the brain and spinal cord, called the meninges. […] It isn’t clear what causes a meningioma. Experts know that something changes some cells in the meninges. The changes makes them multiply out of control. This leads to a meningioma. […] Being exposed to radiation as a child is the only known environmental risk factor for getting meningioma. There’s no good evidence to show that meningiomas happen because of cellphone use.

• #80 Meningioma | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/meningioma?lang=us

  Meningiomas are thought to arise from meningocytes or arachnoid cap cells, which themselves arise from pluripotent mesenchymal progenitor cells, which accounts for the unusual location of primary extradural tumors 17,18. […] Although the majority of tumors are sporadic, they are also seen in the setting of previous cranial irradiation and of course in patients with neurofibromatosis type 2 (Merlin gene on Chromosome 22). Additionally, meningiomas demonstrate estrogen and progesterone sensitivity and may grow during pregnancy. […] The underlying mechanism is most likely multifactorial however it has been shown that there is a strong association between the presence and severity of the peritumoral vasogenic edema (i.e. edema index) and expression of the vascular endothelial growth factor (VEGF) or expression of CEA and CK 16,23.

• #81 Reapprasial of the role of endocrine therapy in meningioma management in: Endocrine-Related Cancer Volume 15 Issue 4 (2008)

  https://erc.bioscientifica.com/view/journals/erc/15/4/931.xml

  The aetiology of primary brain tumours remains a controversial issue and the only somewhat well-established risk factors for meningioma are ionizing radiation. […] The correlation between breast cancer and meningioma raises the question of a common pathogenic mechanism. […] It remains difficult to interpret the results from epidemiological trials that are most often biased and retrospectively analysed. […] Understanding of pathways of steroid-mediated transactivation should allow new approaches in the treatment of meningiomas in order to improve the patients’ outcome. […] Although the underlying genetic causes are unknown, meningiomas’ growth is sustained by the dysregulated expression of steroid hormones, growth factors, their receptors and activation of signal transduction cascades.

• #82 Atypical Meningioma in a Young HIV Patient | Abbara | Journal of Medical Cases

  https://www.journalmc.org/index.php/JMC/article/view/40/32

  Meningiomas represent 33.4% of all primary brain tumors, making them the most common primary brain tumors. […] Approximately 90% of meningiomas are benign, 5-10% atypical [World Health organization (WHO) grade II] and less than 2% classified as malignant (WHO grade III, also termed anaplastic). […] In HIV positive patients, not all intracranial cysto-necrotic brain lesions are indicative of an infectious process. They may be a tumor manifestation, including meningiomas. Viral antigens, like HIV tat protein, have been implicated in the pathogenesis of such tumors. […] It may be that the HIV virus plays an oncogenic role through the occurrence of mutations and especially loss of chromosome 22 on a background of immune deficiency. […] This case suggests that HIV positive patients may develop higher malignancy meningiomas at an earlier age than in the general population where it occurs usually at age 55 years for atypical meningioma.

• #83

  https://journals.lww.com/neur/fulltext/2015/63040/meningiomas_decoded__looking_beyond_microsurgery.10.aspx

  Despite significant advancements in neurosurgical techniques and knowledge of pathogenesis of meningiomas, the treatment of meningiomas continues to stagnate with surgery, radiotherapy, and radiosurgery. […] A plethora of genetic loci have been investigated in the research on atypical and anaplastic meningiomas. Up to 78% of sporadic meningiomas and all NF2-associated meningiomas have allelic losses at 22q12.2. […] Protein 4.1B is considered to be a tumor suppressor and has been implicated in meningioma pathogenesis. […] While aberrations in 22q and protein 4.1 family are responsible for the genesis of meningiomas, the driving factor behind progression of meningiomas to higher grades is obscure, but accumulation of chromosomal losses and gains has been suspected to offer a growth advantage.

• #84

  https://journals.lww.com/neur/fulltext/2015/63040/meningiomas_decoded__looking_beyond_microsurgery.10.aspx

  Candidate gene targets including CDKN2C, RAD54 L, EPB41, GADD45A, and ALPL have been extensively investigated, but a cause-effect relationship has failed to emerge. […] Mutation of the human telomerase reverses transcriptase reactivates telomerase activity and sustains cell division and is found in up to 92% of atypical and 100% of anaplastic meningiomas. […] The role of these genes in tumor progression to higher grades is yet to be fully ascertained. […] These chromosomal aberrations induce tumor progression to higher grades through signaling pathways. […] The NF2 gene as the initiator of tumorigenesis and accumulation of mutations leading to progression of meningiomas to higher grades has been clearly demonstrated.

• #85

  https://journals.lww.com/neur/fulltext/2015/63040/meningiomas_decoded__looking_beyond_microsurgery.10.aspx

  Despite significant advancements in neurosurgical techniques and knowledge of pathogenesis of meningiomas, the treatment of meningiomas continues to stagnate with surgery, radiotherapy, and radiosurgery. […] A plethora of genetic loci have been investigated in the research on atypical and anaplastic meningiomas. Up to 78% of sporadic meningiomas and all NF2-associated meningiomas have allelic losses at 22q12.2. […] Protein 4.1B is considered to be a tumor suppressor and has been implicated in meningioma pathogenesis. […] While aberrations in 22q and protein 4.1 family are responsible for the genesis of meningiomas, the driving factor behind progression of meningiomas to higher grades is obscure, but accumulation of chromosomal losses and gains has been suspected to offer a growth advantage.

• #86

  https://journals.lww.com/neur/fulltext/2015/63040/meningiomas_decoded__looking_beyond_microsurgery.10.aspx

  Despite significant advancements in neurosurgical techniques and knowledge of pathogenesis of meningiomas, the treatment of meningiomas continues to stagnate with surgery, radiotherapy, and radiosurgery. […] A plethora of genetic loci have been investigated in the research on atypical and anaplastic meningiomas. Up to 78% of sporadic meningiomas and all NF2-associated meningiomas have allelic losses at 22q12.2. […] Protein 4.1B is considered to be a tumor suppressor and has been implicated in meningioma pathogenesis. […] While aberrations in 22q and protein 4.1 family are responsible for the genesis of meningiomas, the driving factor behind progression of meningiomas to higher grades is obscure, but accumulation of chromosomal losses and gains has been suspected to offer a growth advantage.

• #87

  https://journals.lww.com/neur/fulltext/2015/63040/meningiomas_decoded__looking_beyond_microsurgery.10.aspx

  Candidate gene targets including CDKN2C, RAD54 L, EPB41, GADD45A, and ALPL have been extensively investigated, but a cause-effect relationship has failed to emerge. […] Mutation of the human telomerase reverses transcriptase reactivates telomerase activity and sustains cell division and is found in up to 92% of atypical and 100% of anaplastic meningiomas. […] The role of these genes in tumor progression to higher grades is yet to be fully ascertained. […] These chromosomal aberrations induce tumor progression to higher grades through signaling pathways. […] The NF2 gene as the initiator of tumorigenesis and accumulation of mutations leading to progression of meningiomas to higher grades has been clearly demonstrated.

• #88 Meningioma recurrence

  https://www.degruyter.com/document/doi/10.1515/med-2016-0032/html?lang=en

  Meningioma is also a component of numerous familiar tumour syndromes. […] A novel avenue to an understanding of meningioma pathogenesis is research into epigenetic mechanisms. […] Although NF2 is relatively frequently mutated in meningioma, epigenetic alteration of NF2 is rare. […] The third major epigenetic factor, micro RNAs (miRNAs), are important in regulating post-translational silencing. […] The clinical behaviour and risk of recurrence have a very close association with the histological grade of the tumour. […] Several studies have proven the close association between histological grade and risk of recurrence. […] The extent of resection is graded according to Simpson, using a 5-tier scale. […] There is close correlation between Simpson grade and risk of recurrence. […] In higher Simpson grades (III-V) disease-free survival is shorter, quality of life is reduced, and there is an increased chance of early recurrence of the tumour. […] Although meningiomas are tumours that occur with high frequency, the mechanisms underlying pathogenesis, recurrence, and progression remain poorly understood.

• #89 Meningioma recurrence

  https://www.degruyter.com/document/doi/10.1515/med-2016-0032/html?lang=en

  Meningioma is also a component of numerous familiar tumour syndromes. […] A novel avenue to an understanding of meningioma pathogenesis is research into epigenetic mechanisms. […] Although NF2 is relatively frequently mutated in meningioma, epigenetic alteration of NF2 is rare. […] The third major epigenetic factor, micro RNAs (miRNAs), are important in regulating post-translational silencing. […] The clinical behaviour and risk of recurrence have a very close association with the histological grade of the tumour. […] Several studies have proven the close association between histological grade and risk of recurrence. […] The extent of resection is graded according to Simpson, using a 5-tier scale. […] There is close correlation between Simpson grade and risk of recurrence. […] In higher Simpson grades (III-V) disease-free survival is shorter, quality of life is reduced, and there is an increased chance of early recurrence of the tumour. […] Although meningiomas are tumours that occur with high frequency, the mechanisms underlying pathogenesis, recurrence, and progression remain poorly understood.

• #90 Meningioma recurrence

  https://www.degruyter.com/document/doi/10.1515/med-2016-0032/html?lang=en

  Meningioma is also a component of numerous familiar tumour syndromes. […] A novel avenue to an understanding of meningioma pathogenesis is research into epigenetic mechanisms. […] Although NF2 is relatively frequently mutated in meningioma, epigenetic alteration of NF2 is rare. […] The third major epigenetic factor, micro RNAs (miRNAs), are important in regulating post-translational silencing. […] The clinical behaviour and risk of recurrence have a very close association with the histological grade of the tumour. […] Several studies have proven the close association between histological grade and risk of recurrence. […] The extent of resection is graded according to Simpson, using a 5-tier scale. […] There is close correlation between Simpson grade and risk of recurrence. […] In higher Simpson grades (III-V) disease-free survival is shorter, quality of life is reduced, and there is an increased chance of early recurrence of the tumour. […] Although meningiomas are tumours that occur with high frequency, the mechanisms underlying pathogenesis, recurrence, and progression remain poorly understood.

• #91 Meningioma recurrence

  https://www.degruyter.com/document/doi/10.1515/med-2016-0032/html?lang=en

  Meningioma is also a component of numerous familiar tumour syndromes. […] A novel avenue to an understanding of meningioma pathogenesis is research into epigenetic mechanisms. […] Although NF2 is relatively frequently mutated in meningioma, epigenetic alteration of NF2 is rare. […] The third major epigenetic factor, micro RNAs (miRNAs), are important in regulating post-translational silencing. […] The clinical behaviour and risk of recurrence have a very close association with the histological grade of the tumour. […] Several studies have proven the close association between histological grade and risk of recurrence. […] The extent of resection is graded according to Simpson, using a 5-tier scale. […] There is close correlation between Simpson grade and risk of recurrence. […] In higher Simpson grades (III-V) disease-free survival is shorter, quality of life is reduced, and there is an increased chance of early recurrence of the tumour. […] Although meningiomas are tumours that occur with high frequency, the mechanisms underlying pathogenesis, recurrence, and progression remain poorly understood.

• #92 Meningioma recurrence

  https://www.degruyter.com/document/doi/10.1515/med-2016-0032/html?lang=en

  Meningioma is also a component of numerous familiar tumour syndromes. […] A novel avenue to an understanding of meningioma pathogenesis is research into epigenetic mechanisms. […] Although NF2 is relatively frequently mutated in meningioma, epigenetic alteration of NF2 is rare. […] The third major epigenetic factor, micro RNAs (miRNAs), are important in regulating post-translational silencing. […] The clinical behaviour and risk of recurrence have a very close association with the histological grade of the tumour. […] Several studies have proven the close association between histological grade and risk of recurrence. […] The extent of resection is graded according to Simpson, using a 5-tier scale. […] There is close correlation between Simpson grade and risk of recurrence. […] In higher Simpson grades (III-V) disease-free survival is shorter, quality of life is reduced, and there is an increased chance of early recurrence of the tumour. […] Although meningiomas are tumours that occur with high frequency, the mechanisms underlying pathogenesis, recurrence, and progression remain poorly understood.

• #93 Molecular pathogenesis of meningiomas – PubMed

  https://pubmed.ncbi.nlm.nih.gov/15674477/

  Meningiomas are common central nervous system tumors that originate from the meningeal coverings of the brain and the spinal cord. […] Current data indicate that meningioma initiation is closely linked to the inactivation of one or more members of the highly conserved protein 4.1 superfamily, including the neurofibromatosis type 2 gene product merlin/schwannomin, protein 4.IB (DAL-1) and protein 4.1R. […] A better understanding of the molecular mechanisms involved in meningioma pathogenesis may not only lead to the identification of novel diagnostic and prognostic marker but will also facilitate the development of new pathogenesis-based therapeutic strategies.

• #94 (PDF) Molecular pathogenesis of meningiomas

  https://www.academia.edu/113491290/Molecular_pathogenesis_of_meningiomas?uc-sb-sw=7828342

  Significant progress has been made in recent years in delineating the molecular mechanisms involved in meningioma formation, growth, and malignant progression. However, many questions remain unanswered. Mutations in the NF2 gene probably account for the formation of more than half of all meningiomas. On the other hand, the molecular events underlying the initiation of meningiomas without NF2 mutations have yet to be identified. Investigating hereditary conditions associated with an increased meningioma incidence and the mechanisms underlying the development of radiation-induced meningiomas could potentially yield relevant insights. Meningioma growth is sustained by the dysregulated expression of steroid hormones, growth factors , their receptors, and activation of signal transduction cascades. The underlying genetic causes are unknown. Malignant progression of meningiomas probably involves the inactivation of tumor suppressor genes on chromosomes 1p, 9p, 10q, and 14q. However, with the possible exception of INK4A/INK4B, the actual targets of these chromosomal losses have remained largely elusive.

• #95 The molecular genetics and tumor pathogenesis of meningiomas and the future directions of meningioma treatments in: Neurosurgical Focus Volume 30 Issue 5 (2011) Journals

  https://thejns.org/focus/view/journals/neurosurg-focus/30/5/2011.2.focus1116.xml

  Studies have also implicated a myriad of aberrant signaling pathways involved with meningioma tumorigenesis, including those involved with proliferation, angiogenesis, and autocrine loops. Understanding these disrupted pathways will aid in deciphering the relationship between various genetic changes and their downstream effects on meningioma pathogenesis. […] Despite advancements in our understanding of meningioma pathogenesis, the conventional treatments, including surgery, radiotherapy, and stereotactic radiosurgery, have remained largely stagnant. Surgery and radiation therapy are curative in the majority of lesions, yet treatment remains challenging for meningiomas that are recurrent, aggressive, or refractory to conventional treatments. Future therapies will include combinations of targeted molecular agents as a result of continued progress in the understanding of genetic and biological changes associated with meningiomas.

• #96 The molecular genetics and tumor pathogenesis of meningiomas and the future directions of meningioma treatments in: Neurosurgical Focus Volume 30 Issue 5 (2011) Journals

  https://thejns.org/focus/view/journals/neurosurg-focus/30/5/2011.2.focus1116.xml

  Studies have also implicated a myriad of aberrant signaling pathways involved with meningioma tumorigenesis, including those involved with proliferation, angiogenesis, and autocrine loops. Understanding these disrupted pathways will aid in deciphering the relationship between various genetic changes and their downstream effects on meningioma pathogenesis. […] Despite advancements in our understanding of meningioma pathogenesis, the conventional treatments, including surgery, radiotherapy, and stereotactic radiosurgery, have remained largely stagnant. Surgery and radiation therapy are curative in the majority of lesions, yet treatment remains challenging for meningiomas that are recurrent, aggressive, or refractory to conventional treatments. Future therapies will include combinations of targeted molecular agents as a result of continued progress in the understanding of genetic and biological changes associated with meningiomas.

• #97 The molecular genetics and tumor pathogenesis of meningiomas and the future directions of meningioma treatments in: Neurosurgical Focus Volume 30 Issue 5 (2011) Journals

  https://thejns.org/focus/view/journals/neurosurg-focus/30/5/2011.2.focus1116.xml

  Studies have also implicated a myriad of aberrant signaling pathways involved with meningioma tumorigenesis, including those involved with proliferation, angiogenesis, and autocrine loops. Understanding these disrupted pathways will aid in deciphering the relationship between various genetic changes and their downstream effects on meningioma pathogenesis. […] Despite advancements in our understanding of meningioma pathogenesis, the conventional treatments, including surgery, radiotherapy, and stereotactic radiosurgery, have remained largely stagnant. Surgery and radiation therapy are curative in the majority of lesions, yet treatment remains challenging for meningiomas that are recurrent, aggressive, or refractory to conventional treatments. Future therapies will include combinations of targeted molecular agents as a result of continued progress in the understanding of genetic and biological changes associated with meningiomas.

• #98 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  MAPKs are intracellular serine/threonine-specific protein kinases which are activated by extracellular stimuli (e.g., mitogen signals), leading to sequential activation of a kinase cascade triggered by the Ras/Raf-1/MEK-1/MAPK/ERK pathway and that ultimately, leads to phosphorylation/activation of transcription factors in the nucleus. […] PI3Ks are a family of intracellular signal transducer enzymes that phosphorylate inositol phospholipids. […] Activation of PI3K results in phosphorylation/activation of PKB/Akt and subsequently p70S6K, which are key elements of the cell growth-promoting effects of this pathway; alternatively, activating mutations of AKT have also been recently reported in a subset of meningiomas. […] In line with this, Johnson et al. found evidences for the activation of both the MAPK and the Akt/PKB pathways in meningiomas, upon growth factor receptor signaling via e.g. PDGF-BB and PDGF; furthermore, these authors showed that administration of MAPK or PI3K inhibitors induces progressive growth inhibition of meningioma cells in association with reduced phosphorylation of MAPK or Akt and p70S6K, respectively.

• #99 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  MAPKs are intracellular serine/threonine-specific protein kinases which are activated by extracellular stimuli (e.g., mitogen signals), leading to sequential activation of a kinase cascade triggered by the Ras/Raf-1/MEK-1/MAPK/ERK pathway and that ultimately, leads to phosphorylation/activation of transcription factors in the nucleus. […] PI3Ks are a family of intracellular signal transducer enzymes that phosphorylate inositol phospholipids. […] Activation of PI3K results in phosphorylation/activation of PKB/Akt and subsequently p70S6K, which are key elements of the cell growth-promoting effects of this pathway; alternatively, activating mutations of AKT have also been recently reported in a subset of meningiomas. […] In line with this, Johnson et al. found evidences for the activation of both the MAPK and the Akt/PKB pathways in meningiomas, upon growth factor receptor signaling via e.g. PDGF-BB and PDGF; furthermore, these authors showed that administration of MAPK or PI3K inhibitors induces progressive growth inhibition of meningioma cells in association with reduced phosphorylation of MAPK or Akt and p70S6K, respectively.

• #100 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  VEGFA and its VEGFR-1 receptor have been associated with regulation of the development of new blood vessels and peritumoral edema in brain tumors, a common feature in meningioma patients. […] Of note, meningiomas express both VEGF and VEGFR, and VEGF expression correlates with the severity of peritumoral edema and tumor vascularization. […] Despite this, the precise mechanisms that regulate VEGF expression in meningiomas remain unknown. […] In human cells, VEGF is mainly regulated by the hypoxia inducible factor-1 (HIF-1) transcription factor and in meningiomas, HIF-1 expression correlates with VEGF expression and the degree of peritumoral edema. […] In addition, upregulation of VEGF expression can also be induced by other growth factors such as EGF and PDGF, suggesting that both growth factors and hypoxia stimulation may all contribute to control VEGF expression in these tumors.

• #101 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  The wingless (wnt)/-catenin pathway has also been implicated in meningioma progression, through an altered expression of several of its genes. […] Thus, early studies based on microarray gene expression profiling identified increased expression of genes such as CTNNB1, CDK5R1, ENC1 and CCND1. […] Subsequently, Pecina-Slaus et al. reported LOH of the E-cadherin (CDH1) and the adenomatous polyposis coli (APC) tumor suppressor genes in about one-third and half of the cases, respectively. […] Downregulation of E-cadherin expression in clinically aggressive and invasive meningiomas had already been described in association with upregulation and nuclear/perinuclear localization of -catenin, suggesting an important role for the WNT/ catenin pathway in meningioma tumorigenesis. […] Interestingly, Zhou et al. suggested a model in which active merlin would inhibit Wnt/-catenin signaling and maintain -catenin and N-cadherin complexed at the plasma membrane; loss of merlin would then lead to loss of contact inhibition and activation of Wnt/-catenin signaling, translocation of -catenin to the nucleus and expression of intracellular growth-associated proteins such as c-myc and cyclin D1.

• #102 Meningioma Genomics: Gene Discovery, Molecular Mechanisms, And Clinical Correlations

  https://elischolar.library.yale.edu/ymtdl/3433/

  We demonstrate elevated H3K27me3 signal and concordantly decreased gene expression in SWI/SNF-mutant meningiomas, suggesting increased PRC2 activity either by decreased inhibition (loss-of-function) or potentiation (neomorphic function) by mutant SWI/SNF. Inhibitors of EZH2, the H3K27me3 catalytic subunit of PRC2, may thus prove efficacious in SWI/SNF-mutant meningiomas. […] In conclusion, this study identifies additional novel candidate meningioma driver mutations in SWI/SNF subunits, proposes a molecular mechanism underlying SWI/SNF-mutant meningiomas, and reveals novel genomic-clinical correlations in addition to validating previous associations. Overall, these results may guide future targeted therapies and clinical management to improve the outcomes of patients with meningiomas.

• #103 Genetic/molecular alterations of meningiomas and the signaling pathways targeted | Oncotarget

  https://www.oncotarget.com/article/3870/text/

  Interestingly, recent reports have identified SMO mutations in meningiomas lacking NF2 mutations, which further supports the potentially relevant role of this pathway in the development of at least some meningiomas. […] Based on all what has been described above, at present it is well-established that meningiomas are cytogenetically heterogenous tumors. […] Consequently, for decades now, attempts have been made to classify meningiomas on cytogenetic grounds. […] The first cytogenetic classifications and cytogenetic models of progression of meningiomas were proposed in the 1990s. […] Weber et al. proposed a model of genomic alterations associated with meningioma progression based on comparative genomic hybridization (CGH) analysis of tumors of different grades. […] Later on, Ketter et al. and Zang et al., subdivided meningiomas into four subgroups based on their cytogenetic findings: Group 0, included meningiomas with a normal diploid chromosomal set; Group 1, consisted of tumors with monosomy 22 as the sole cytogenetic alteration; Group 2, was composed of tumors showing marked hypodiploidy with loss of additional autosomes, and finally; Group 3 included meningiomas with deletions of the short arm of chromosome 1, in association with other chromosomal aberrations such as loss of chromosome 22.

• #104 Meningioma: The Unusual Growth in a Transsexual Patient after Estrogen-Progesterone Therapy

  https://symbiosisonlinepublishing.com/neurology/neurology09.php

  The frequency of meningioma is nearly twice as high in females as in males. This difference in incidence is partly explained by molecular and immunehistochemical studies indicating that meningioma is sensitive to hormones. Approximately 70% of meningiomas express progesterone receptors and 30% express estrogen receptors. It has also been observed that meningioma cells tend to proliferate when exposed to estrogen and progesterone. […] More detailed molecular and immunohistochemical research provides evidence that meningiomas are hormone-sensitive tumors, with 70% of cells expressing progesterone receptors and around 30% expressing estrogen receptors. Many of these studies also report that human meningioma cells proliferate when exposed to progesterone and estrogen. Most meningiomas express functional progesterone rather than estrogen receptors and show growth during the progesterone-predominant luteal phase.

• #105 A Review of Recurrent Meningiomas with Prolonged Response to Cabozantinib, an Oral Multitarget Tyrosine Kinase Inhibitor

  https://www.sysrevpharm.org/articles/a-review-of-recurrent-meningiomas-with-prolonged-response-to-cabozantinib-an-oral-multitarget-tyrosine-kinase-inhibitor-103382.html

  Meningiomas are cerebral cancers that arise from abnormal cell development in the meninges and defensive layers covering the mind and spinal line. […] Recent advances in atomic science and genomics have revealed insights into the fundamental sub-atomic adjustments and flagging pathways involved in the improvement of meningoma. […] These revelations have opened new roads for designated treatments that plan to disturb explicit sub-atomic targets odpowiedzialne za cancer development and movement. […] Cabozantinib applies its pharmacological impacts by restraining numerous receptor tyrosine kinases, including Vascular Endothelial Development Factor Receptor 2 (VEGFR2), Mesenchymal Epithelial Transition (MET), and Anexelekto (AXL). […] The restraint of these flagging pathways has been related to cancer impacts in different malignancies, making cabozantinib an alluring contender for meningioma therapy.

• #106 A Review of Recurrent Meningiomas with Prolonged Response to Cabozantinib, an Oral Multitarget Tyrosine Kinase Inhibitor

  https://www.sysrevpharm.org/articles/a-review-of-recurrent-meningiomas-with-prolonged-response-to-cabozantinib-an-oral-multitarget-tyrosine-kinase-inhibitor-103382.html

  Recent advances in atomic science and genomics have revealed insights into the fundamental sub-atomic adjustments and flagging pathways involved in meningioma improvement. […] Understanding the pathophysiology of intracranial meningiomas is essential for the advancement of designated treatments and development of treatment results. […] Progress in atomic science and hereditary qualities has provided significant knowledge of the fundamental komponenty meningioma improvement, prompting possible restorative targets and personalized treatment. […] The dysregulation of the mammalian Target of Rapamycin (mTOR) pathway is habitually seen in meningiomas and offers a promising remedial objective. […] Cabozantinib inhibits tumor angiogenesis through its inhibitory effects on VEGFR signaling through multiple pathways.

• #107 A Review of Recurrent Meningiomas with Prolonged Response to Cabozantinib, an Oral Multitarget Tyrosine Kinase Inhibitor

  https://www.sysrevpharm.org/articles/a-review-of-recurrent-meningiomas-with-prolonged-response-to-cabozantinib-an-oral-multitarget-tyrosine-kinase-inhibitor-103382.html

  Cabozantinib disrupts various angiogenesis-related downstream signaling pathways as a result of its inhibition of VEGFR. […] Cabozantinib effectively disrupts VEGFR signaling through these multiple inhibition pathways, reducing tumor angiogenesis. […] Cabozantinib inhibits MET signaling, a receptor tyrosine kinase that is involved in the survival, invasion, and metastasis of tumor cells. […] Cabozantinib inhibits specific cellular pathways in meningiomas by inhibiting the MET and VEGFR2 signaling pathways. […] The activation of the MET pathway has been observed in meningiomas and has been linked to tumor growth and invasion. […] The infiltrative growth pattern of meningiomas makes it difficult to treat them effectively because of their invasive nature. […] The production of pro-angiogenic factors, such as Vascular Endothelial Growth Factor (VEGF), which encourage the formation of new blood vessels in the tumor microenvironment, is sped up when MET is activated.

• #108 Challenges and Opportunities in Future Meningioma Research and Care | Neupsy Key

  https://neupsykey.com/challenges-and-opportunities-in-future-meningioma-research-and-care/

  Our current understanding on the molecular oncogenesis of meningiomas is still very immature. A clonal origin and a stepwise progression to more malignant forms have been suggested by molecular biological studies in the last few decades. However, the origins of the initiation, persistence, and progression of oncogenesis are still not known. […] What is the role of sex hormone receptors in meningioma pathogenesis? […] What is the role of genes other than those on chromosome 22 in initiating meningiomas and driving them to progress? […] Meningiomas are very vascular tumors and their growth is very much influenced by their vascular supply? Our current understanding of the angiogenetic potential of meningiomas and the role of antiangiogenic therapies remains limited. […] The INTERPHONE study is the largest case control study to date to examine the risks of mobile-phone use and includes more than 2400 meningioma cases. Also in 2005, the NIH funded a very large study led by Dr. Elizabeth Claus, which will begin to answer several ongoing questions in meningioma pathogenesis: What effects do pregnancy, oral contraceptives, and hormone replacement therapy have on meningioma formation? Is cell phone use related to meningioma development?

• #109 Challenges and Opportunities in Future Meningioma Research and Care | Neupsy Key

  https://neupsykey.com/challenges-and-opportunities-in-future-meningioma-research-and-care/

  Our current understanding on the molecular oncogenesis of meningiomas is still very immature. A clonal origin and a stepwise progression to more malignant forms have been suggested by molecular biological studies in the last few decades. However, the origins of the initiation, persistence, and progression of oncogenesis are still not known. […] What is the role of sex hormone receptors in meningioma pathogenesis? […] What is the role of genes other than those on chromosome 22 in initiating meningiomas and driving them to progress? […] Meningiomas are very vascular tumors and their growth is very much influenced by their vascular supply? Our current understanding of the angiogenetic potential of meningiomas and the role of antiangiogenic therapies remains limited. […] The INTERPHONE study is the largest case control study to date to examine the risks of mobile-phone use and includes more than 2400 meningioma cases. Also in 2005, the NIH funded a very large study led by Dr. Elizabeth Claus, which will begin to answer several ongoing questions in meningioma pathogenesis: What effects do pregnancy, oral contraceptives, and hormone replacement therapy have on meningioma formation? Is cell phone use related to meningioma development?

• #110 Challenges and Opportunities in Future Meningioma Research and Care | Neupsy Key

  https://neupsykey.com/challenges-and-opportunities-in-future-meningioma-research-and-care/

  Our current understanding on the molecular oncogenesis of meningiomas is still very immature. A clonal origin and a stepwise progression to more malignant forms have been suggested by molecular biological studies in the last few decades. However, the origins of the initiation, persistence, and progression of oncogenesis are still not known. […] What is the role of sex hormone receptors in meningioma pathogenesis? […] What is the role of genes other than those on chromosome 22 in initiating meningiomas and driving them to progress? […] Meningiomas are very vascular tumors and their growth is very much influenced by their vascular supply? Our current understanding of the angiogenetic potential of meningiomas and the role of antiangiogenic therapies remains limited. […] The INTERPHONE study is the largest case control study to date to examine the risks of mobile-phone use and includes more than 2400 meningioma cases. Also in 2005, the NIH funded a very large study led by Dr. Elizabeth Claus, which will begin to answer several ongoing questions in meningioma pathogenesis: What effects do pregnancy, oral contraceptives, and hormone replacement therapy have on meningioma formation? Is cell phone use related to meningioma development?

• #111 Challenges and Opportunities in Future Meningioma Research and Care | Neupsy Key

  https://neupsykey.com/challenges-and-opportunities-in-future-meningioma-research-and-care/

  Our current understanding on the molecular oncogenesis of meningiomas is still very immature. A clonal origin and a stepwise progression to more malignant forms have been suggested by molecular biological studies in the last few decades. However, the origins of the initiation, persistence, and progression of oncogenesis are still not known. […] What is the role of sex hormone receptors in meningioma pathogenesis? […] What is the role of genes other than those on chromosome 22 in initiating meningiomas and driving them to progress? […] Meningiomas are very vascular tumors and their growth is very much influenced by their vascular supply? Our current understanding of the angiogenetic potential of meningiomas and the role of antiangiogenic therapies remains limited. […] The INTERPHONE study is the largest case control study to date to examine the risks of mobile-phone use and includes more than 2400 meningioma cases. Also in 2005, the NIH funded a very large study led by Dr. Elizabeth Claus, which will begin to answer several ongoing questions in meningioma pathogenesis: What effects do pregnancy, oral contraceptives, and hormone replacement therapy have on meningioma formation? Is cell phone use related to meningioma development?

• #112 Challenges and Opportunities in Future Meningioma Research and Care | Neupsy Key

  https://neupsykey.com/challenges-and-opportunities-in-future-meningioma-research-and-care/

  Our current understanding on the molecular oncogenesis of meningiomas is still very immature. A clonal origin and a stepwise progression to more malignant forms have been suggested by molecular biological studies in the last few decades. However, the origins of the initiation, persistence, and progression of oncogenesis are still not known. […] What is the role of sex hormone receptors in meningioma pathogenesis? […] What is the role of genes other than those on chromosome 22 in initiating meningiomas and driving them to progress? […] Meningiomas are very vascular tumors and their growth is very much influenced by their vascular supply? Our current understanding of the angiogenetic potential of meningiomas and the role of antiangiogenic therapies remains limited. […] The INTERPHONE study is the largest case control study to date to examine the risks of mobile-phone use and includes more than 2400 meningioma cases. Also in 2005, the NIH funded a very large study led by Dr. Elizabeth Claus, which will begin to answer several ongoing questions in meningioma pathogenesis: What effects do pregnancy, oral contraceptives, and hormone replacement therapy have on meningioma formation? Is cell phone use related to meningioma development?

• #113 Pathophysiology of meningioma growth in pregnancy

  https://www.degruyter.com/document/doi/10.1515/med-2017-0029/html?lang=en

  Meningioma is among the most frequent brain tumours predominantly affecting elderly women. […] The biological behaviour of meningioma in pregnancy is different from other meningiomas. […] The possible explanation is rooted in the complex physiological changes and hormonal differences during pregnancy. […] The increased meningioma growth observed in pregnancy is presumably the result of endocrine mechanisms. […] These include increase in progesterone, human placental lactogen (hPL) and prolactin (PRL) serum levels. […] The background of the complex pathophysiological and morphological changes in tumours in pregnancy are far from being understood. […] It has been shown that meningioma growth is enhanced in the progesterone-dominated luteal phase of the menstrual cycle. […] The changes of plasma concentration of the above mentioned hormones during pregnancy and their effect on meningioma growth are in concert with the notion, that regarding tumour (including meningioma) growth the second and third trimester are crucial and critical.

• #114 Meningioma Genomics: Gene Discovery, Molecular Mechanisms, And Clinical Correlations

  https://elischolar.library.yale.edu/ymtdl/3433/

  Meningiomas, the most common primary intracranial tumors, can cause significant morbidity and mortality, requiring novel targeted therapies. The genomic basis of approximately 80% of sporadic meningiomas has recently been established, however, the rest remain mutation-unknown. Identification of additional driver and/or co-driver genes could guide future targeted therapies. […] Recently established is the distinct subgroup of meningiomas harboring mutations in the SMARCB1 tumor suppressor gene, a core subunit of the SWI/SNF chromatin-remodeling complex. Notably, SWI/SNF mutations in other tumors have been associated with dysregulation of the PRC2 complex, an epigenetic regulator whose signature marker of activity is H3K27me3. However, the molecular mechanism of tumorigenesis in SWI/SNF-mutant meningiomas remains unknown, limiting options for targeted therapies.

• #115 Nanomedicine and gene therapy for meningioma treatment – UQ–IITD : UQ–IITD –

  https://uqiitd.org/projects/nanomedicine-and-gene-therapy-for-meningioma-treatment/

  Meningioma is one of the most common central nervous system (CNS) tumors, comprising around 38.3% of all primary brain tumors. […] There is, thus, a pressing need to understand the molecular biology of meningioma pathogenesis and devise novel therapies. […] There is no targeted systemic therapy currently available for meningioma. Thus, there is a dire need to thoroughly understand the molecular biology of meningioma pathogenesis and find new therapeutic targets. […] The proposed research aims to improve the quality of care and quality of life for meningioma patients by developing new, potentially curative therapies, specially for high grade and recurrent meningiomas that have become refractory to conventional treatments.

• #116 Nanomedicine and gene therapy for meningioma treatment – UQ–IITD : UQ–IITD –

  https://uqiitd.org/projects/nanomedicine-and-gene-therapy-for-meningioma-treatment/

  Meningioma is one of the most common central nervous system (CNS) tumors, comprising around 38.3% of all primary brain tumors. […] There is, thus, a pressing need to understand the molecular biology of meningioma pathogenesis and devise novel therapies. […] There is no targeted systemic therapy currently available for meningioma. Thus, there is a dire need to thoroughly understand the molecular biology of meningioma pathogenesis and find new therapeutic targets. […] The proposed research aims to improve the quality of care and quality of life for meningioma patients by developing new, potentially curative therapies, specially for high grade and recurrent meningiomas that have become refractory to conventional treatments.

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

  https://www.mdpi.com/2227-9059/9/3/319

  Advances in molecular techniques over the last decade that include genomic and epigenomic data associated with meningiomas have been used to identify genetic biomarkers that may predict tumor behavior and prognosis. […] Chromosomal instability has repeatedly been shown to be one of the most frequent molecular alterations for tumor recurrence and prognosis. Accumulation of cytogenetic aberrations correlates with increasing tumor grades and aggressiveness, with higher-grade (atypical and anaplastic) meningiomas demonstrating an increasingly complex cytogenetic profile compared to benign meningiomas. […] While the majority of meningiomas occurs sporadically, there are many rare familial syndromes that increase the risk of developing these tumors. While exact molecular mechanisms have yet to be elucidated, these familial syndromes might provide insight behind sporadic meningioma tumorigenesis and implications for management.

• #118 Review of meningioma diagnosis and management | Egyptian Journal of Neurosurgery | Full Text

  https://ejns.springeropen.com/articles/10.1186/s41984-023-00195-z

  The grading also changed from the use of Roman numerals to Arabic numerals to align CNS tumors with other systems. […] The characterization of recurrence rates of meningiomas has a high correlation with the Simpson Grading. […] For total surgical resection, the tumor and its dural base are removed. Resection of the dura was found to be important for the prevention of recurrence. […] With the development of monoclonal antibody-based pharmacotherapies that effectively treat other oncologic conditions, there have been a host of new cell cycle regulators and antibody-based drugs which are currently in clinical trials for the treatment and management of varying severities of meningioma. […] Further research and clinical trials of these drugs can revolutionize how we treat and manage meningioma.

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