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Genomic Landscape of Meningiomas

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Biological and Clinical Landscape of Meningiomas

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1416))

Abstract

Despite being the most common primary brain tumor in adults, until recently, the genomics of meningiomas have remained quite understudied. In this chapter we will discuss the early cytogenetic and mutational changes uncovered in meningiomas, from the discovery of the loss of chromosome 22q and the neurofibromatosis-2 (NF2) gene to other non-NF2 driver mutations (KLF4, TRAF7, AKT1, SMO, etc.) discovered using next generation sequencing. We discuss each of these alterations in the context of their clinical significance and conclude the chapter by reviewing recent multiomic studies that have integrated our knowledge of these alterations together to develop novel molecular classifications for meningiomas. 

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References

  1. Ostrom QT, Cioffi G, Waite K, Kruchko C, Barnholtz-Sloan JS. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2014-2018. Neuro Oncol. 2021 Oct 5;23(12 Suppl 2):iii1-iii105. https://doi.org/10.1093/neuonc/noab200. PMID: 34608945; PMCID: PMC8491279.

  2. Chamoun R, Krisht KM, Couldwell WT. Incidental meningiomas. Neurosurgical focus. 2011; 31(6):E19.

    Article  PubMed  Google Scholar 

  3. Saraf S, McCarthy BJ, Villano JL. Update on meningiomas. The oncologist. 2011; 16(11):1604.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Goldbrunner R, Minniti G, Preusser M, et al. EANO guidelines for the diagnosis and treatment of meningiomas. The Lancet Oncology. 2016; 17(9):e383-e391.

    Article  PubMed  Google Scholar 

  5. Gallagher MJ, Jenkinson MD, Brodbelt AR, Mills SJ, Chavredakis E. WHO grade 1 meningioma recurrence: Are location and Simpson grade still relevant? Clinical neurology and neurosurgery. 2016; 141:117-121.

    Article  PubMed  Google Scholar 

  6. Riemenschneider MJ, Perry A, Reifenberger G. Histological classification and molecular genetics of meningiomas. The Lancet Neurology. 2006; 5(12):1045-1054.

    Article  CAS  PubMed  Google Scholar 

  7. Whittle IR, Smith C, Navoo P, Collie D. Meningiomas. The Lancet. 2004; 363(9420):1535-1543.

    Article  Google Scholar 

  8. Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta neuropathologica. 2016; 131(6):803-820.

    Article  PubMed  Google Scholar 

  9. Louis DN, Perry A, Wesseling P, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021; 23(8):1231-1251.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Nanda A, Bir SC, Maiti TK, Konar SK, Missios S, Guthikonda B. Relevance of Simpson grading system and recurrence-free survival after surgery for World Health Organization Grade I meningioma. Journal of neurosurgery. 2017; 126(1):201-211.

    Article  PubMed  Google Scholar 

  11. Vaubel RA, Chen SG, Raleigh DR, et al. Meningiomas with rhabdoid features lacking other histologic features of malignancy: a study of 44 cases and review of the literature. Journal of Neuropathology & Experimental Neurology. 2016; 75(1):44-52.

    Article  Google Scholar 

  12. Jenkinson MD, Santarius T, Zadeh G, Aldape KD. Atypical meningioma—is it time to standardize surgical sampling techniques? Neuro-oncology. 2017; 19(3):453-454.

    PubMed  Google Scholar 

  13. Olar A, Wani KM, Sulman EP, et al. Mitotic index is an independent predictor of recurrence-free survival in meningioma. Brain pathology. 2015; 25(3):266-275.

    Article  PubMed  Google Scholar 

  14. Adeberg S, Hartmann C, Welzel T, et al. Long-term outcome after radiotherapy in patients with atypical and malignant meningiomas—clinical results in 85 patients treated in a single institution leading to optimized guidelines for early radiation therapy. International Journal of Radiation Oncology* Biology* Physics. 2012; 83(3):859-864.

    Google Scholar 

  15. Adegbite AB, Khan MI, Paine KW, Tan LK. The recurrence of intracranial meningiomas after surgical treatment. Journal of neurosurgery. 1983; 58(1):51-56.

    Article  CAS  PubMed  Google Scholar 

  16. Nassiri F, Mamatjan Y, Suppiah S, et al. DNA methylation profiling to predict recurrence risk in meningioma: development and validation of a nomogram to optimize clinical management. Neuro-oncology. 2019; 21(7):901-910.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Suppiah S, Nassiri F, Bi WL, et al. Molecular and translational advances in meningiomas. Neuro-oncology. 2019; 21(Supplement_1):i4-i17.

    Google Scholar 

  18. Sun SQ, Hawasli AH, Huang J, Chicoine MR, Kim AH. An evidence-based treatment algorithm for the management of WHO Grade II and III meningiomas. Neurosurgical focus. 2015; 38(3):E3.

    Article  PubMed  Google Scholar 

  19. Durand A, Labrousse F, Jouvet A, et al. WHO grade II and III meningiomas: a study of prognostic factors. Journal of neuro-oncology. 2009; 95(3):367-375.

    Article  PubMed  Google Scholar 

  20. Rogers L, Gilbert M, Vogelbaum MA. Intracranial meningiomas of atypical (WHO grade II) histology. Journal of neuro-oncology. 2010; 99(3):393-405.

    Article  PubMed  Google Scholar 

  21. Abry E, Thomassen IØ, Salvesen ØO, Torp SH. The significance of Ki-67/MIB-1 labeling index in human meningiomas: a literature study. Pathology-Research and Practice. 2010; 206(12):810-815.

    Article  CAS  PubMed  Google Scholar 

  22. Amatya VJ, Takeshima Y, Sugiyama K, et al. Immunohistochemical study of Ki-67 (MIB-1), p53 protein, p21WAF1, and p27KIP1 expression in benign, atypical, and anaplastic meningiomas. Human pathology. 2001; 32(9):970-975.

    Article  CAS  PubMed  Google Scholar 

  23. Menger R, Connor Jr DE, Chan AY, Jain G, Nanda A. Degree of Resection and Ki-67 Labeling Index for Recurring Meningiomas. Cureus. 2017; 9(11).

    Google Scholar 

  24. Torp S, Lindboe C, Grøberg B, Lydersen S, Sundstrøm S. Prognostic significance of Ki-67/MIB-1 proliferation index in meningiomas. Clinical neuropathology. 2005; 24(4).

    Google Scholar 

  25. Duregon E, Molinaro L, Volante M, et al. Comparative diagnostic and prognostic performances of the hematoxylin-eosin and phospho-histone H3 mitotic count and Ki-67 index in adrenocortical carcinoma. Modern Pathology. 2014; 27(9):1246-1254.

    Article  CAS  PubMed  Google Scholar 

  26. Kim Y-J, Ketter R, Steudel W-I, Feiden W. Prognostic significance of the mitotic index using the mitosis marker anti–phosphohistone H3 in meningiomas. American journal of clinical pathology. 2007; 128(1):118-125.

    Article  CAS  PubMed  Google Scholar 

  27. Uguen A, Conq G, Doucet L, et al. Immunostaining of phospho-histone H3 and Ki-67 improves reproducibility of recurrence risk assessment of gastrointestinal stromal tumors. Virchows Archiv. 2015; 467(1):47-54.

    Article  CAS  PubMed  Google Scholar 

  28. Zack TI, Schumacher SE, Carter SL, et al. Pan-cancer patterns of somatic copy number alteration. Nature genetics. 2013; 45(10):1134-1140.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Zhang Y, Martens JW, Jack XY, et al. Copy number alterations that predict metastatic capability of human breast cancer. Cancer research. 2009; 69(9):3795-3801.

    Article  CAS  PubMed  Google Scholar 

  30. Cheng I, Levin AM, Tai YC, et al. Copy number alterations in prostate tumors and disease aggressiveness. Genes, Chromosomes and Cancer. 2012; 51(1):66-76.

    Article  CAS  PubMed  Google Scholar 

  31. Beroukhim R, Mermel CH, Porter D, et al. The landscape of somatic copy-number alteration across human cancers. Nature. 2010; 463(7283):899-905.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Zang K, Singer H. Chromosomal constitution of meningiomas. Nature. 1967; 216(5110):84-85.

    Article  CAS  PubMed  Google Scholar 

  33. Seizinger BR, De La Monte S, Atkins L, Gusella JF, Martuza RL. Molecular genetic approach to human meningioma: loss of genes on chromosome 22. Proceedings of the National Academy of Sciences. 1987; 84(15):5419-5423.

    Article  CAS  Google Scholar 

  34. Ruttledge MH, Sarrazin J, Rangaratnam S, et al. Evidence for the complete inactivation of the NF2 gene in the majority of sporadic meningiomas. Nature genetics. 1994; 6(2):180-184.

    Article  CAS  PubMed  Google Scholar 

  35. Lee Y, Liu J, Patel S, et al. Genomic landscape of meningiomas. Brain Pathology. 2010; 20(4):751-762.

    Article  CAS  PubMed  Google Scholar 

  36. Bi WL, Greenwald NF, Abedalthagafi M, et al. Genomic landscape of high-grade meningiomas. NPJ genomic medicine. 2017; 2(1):1-14.

    CAS  Google Scholar 

  37. Cai DX, Banerjee R, Scheithauer BW, Lohse CM, Kleinschmidt-Demasters BK, Perry A. Chromosome 1p and 14q FISH analysis in clinicopathologic subsets of meningioma: diagnostic and prognostic implications. Journal of Neuropathology & Experimental Neurology. 2001; 60(6):628-636.

    Article  CAS  Google Scholar 

  38. Lamszus K, Kluwe L, Matschke J, Meissner H, Laas R, Westphal M. Allelic losses at 1p, 9q, 10q, 14q, and 22q in the progression of aggressive meningiomas and undifferentiated meningeal sarcomas. Cancer genetics and cytogenetics. 1999; 110(2):103-110.

    Article  CAS  PubMed  Google Scholar 

  39. Leone PE, Bello MJ, de Campos JM, et al. NF2 gene mutations and allelic status of 1p, 14q and 22q in sporadic meningiomas. Oncogene. 1999; 18(13):2231-2239.

    Article  CAS  PubMed  Google Scholar 

  40. Zang K. Meningioma: a cytogenetic model of a complex benign human tumor, including data on 394 karyotyped cases. Cytogenetic and Genome Research. 2001; 93(3-4):207-220.

    Article  CAS  Google Scholar 

  41. López-Ginés C, Cerdá-Nicolás M, Gil-Benso R, Barcia-Salorio JL, Llombart-Bosch A. Loss of 1p in recurrent meningiomas: a comparative study in successive recurrences by cytogenetics and fluorescence in situ hybridization. Cancer genetics and cytogenetics. 2001; 125(2):119-124.

    Article  PubMed  Google Scholar 

  42. Ketter R, Henn W, Niedermayer I, et al. Predictive value of progression-associated chromosomal aberrations for the prognosis of meningiomas: a retrospective study of 198 cases. Journal of neurosurgery. 2001; 95(4):601-607.

    Article  CAS  PubMed  Google Scholar 

  43. Bello MJ, Pestaña A, Rey JA, et al. Allelic loss at 1 p is associated with tumor progression of meningiomas. Genes, Chromosomes and Cancer. 1994; 9(4):296-298.

    Article  CAS  PubMed  Google Scholar 

  44. Al-Mefty O, Kadri PA, Pravdenkova S, Sawyer JR, Stangeby C, Husain M. Malignant progression in meningioma: documentation of a series and analysis of cytogenetic findings. Journal of neurosurgery. 2004; 101(2):210-218.

    Article  PubMed  Google Scholar 

  45. Aizer AA, Abedalthagafi M, Linda Bi W, et al. A prognostic cytogenetic scoring system to guide the adjuvant management of patients with atypical meningioma. Neuro-oncology. 2015; 18(2):269-274.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Choudhury A, Chen WC, Lucas CG, et al. Hypermitotic meningiomas harbor DNA methylation subgroups with distinct biological and clinical features. Neuro Oncol. 2022.

    Google Scholar 

  47. Yuzawa S, Nishihara H, Yamaguchi S, et al. Clinical impact of targeted amplicon sequencing for meningioma as a practical clinical-sequencing system. Modern pathology. 2016; 29(7):708-716.

    Article  CAS  PubMed  Google Scholar 

  48. Deprez RHL, Bianchi AB, Groen NA, et al. Frequent NF2 gene transcript mutations in sporadic meningiomas and vestibular schwannomas. American journal of human genetics. 1994; 54(6):1022.

    PubMed Central  Google Scholar 

  49. Brastianos PK, Horowitz PM, Santagata S, et al. Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations. Nature genetics. 2013; 45(3):285-289.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Clark VE, Harmancı AS, Bai H, et al. Recurrent somatic mutations in POLR2A define a distinct subset of meningiomas. Nature genetics. 2016; 48(10):1253-1259.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Stamenkovic I, Yu Q. Merlin, a “magic” linker between the extracellular cues and intracellular signaling pathways that regulate cell motility, proliferation, and survival. Current Protein and Peptide Science. 2010; 11(6):471-484.

    Article  CAS  PubMed  Google Scholar 

  52. Hamaratoglu F, Willecke M, Kango-Singh M, et al. The tumour-suppressor genes NF2/Merlin and Expanded act through Hippo signalling to regulate cell proliferation and apoptosis. Nature cell biology. 2006; 8(1):27-36.

    Article  CAS  PubMed  Google Scholar 

  53. Bleeker F, Felicioni L, Buttitta F, et al. AKT1 E17K in human solid tumours. Oncogene. 2008; 27(42):5648-5650.

    Article  CAS  PubMed  Google Scholar 

  54. Tetreault M-P, Yang Y, Katz JP. Krüppel-like factors in cancer. Nature Reviews Cancer. 2013; 13(10):701.

    Article  CAS  PubMed  Google Scholar 

  55. Moyhuddin A, Baser M, Watson C, et al. Somatic mosaicism in neurofibromatosis 2: prevalence and risk of disease transmission to offspring. Journal of medical genetics. 2003; 40(6):459-463.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Clark VE, Erson-Omay EZ, Serin A, et al. Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO. Science. 2013; 339(6123):1077-1080.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Yuzawa S, Nishihara H, Tanaka S. Genetic landscape of meningioma. Brain tumor pathology. 2016; 33(4):237-247.

    Article  CAS  PubMed  Google Scholar 

  58. Mawrin C, Perry A. Pathological classification and molecular genetics of meningiomas. Journal of neuro-oncology. 2010; 99(3):379-391.

    Article  CAS  PubMed  Google Scholar 

  59. Choy W, Kim W, Nagasawa D, et al. The molecular genetics and tumor pathogenesis of meningiomas and the future directions of meningioma treatments. Neurosurgical focus. 2011; 30(5):E6.

    Article  PubMed  Google Scholar 

  60. Shapiro IM, Kolev VN, Vidal CM, et al. Merlin deficiency predicts FAK inhibitor sensitivity: a synthetic lethal relationship. Science translational medicine. 2014; 6(237):237ra268-237ra268.

    Google Scholar 

  61. Sulzmaier FJ, Jean C, Schlaepfer DD. FAK in cancer: mechanistic findings and clinical applications. Nature reviews cancer. 2014; 14(9):598-610.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Owens LV, Xu L, Dent GA, et al. Focal adhesion kinase as a marker of invasive potential in differentiated human thyroid cancer. Annals of Surgical Oncology. 1996; 3(1):100-105.

    Article  CAS  PubMed  Google Scholar 

  63. Tremblay L, Hauck W, Aprikian AG, Begin LR, Chapdelaine A, Chevalier S. Focal adhesion kinase (pp125FAK) expression, activation and association with paxillin and p50CSK in human metastatic prostate carcinoma. International Journal of Cancer. 1996; 68(2):164-171.

    Article  CAS  PubMed  Google Scholar 

  64. McCormack SJ, Brazinski SE, Moore Jr JL, Werness BA, Goldstein DJ. Activation of the focal adhesion kinase signal transduction pathway in cervical carcinoma cell lines and human genital epithelial cells immortalized with human papillomavirus type 18. Oncogene. 1997; 15(3):265-274.

    Article  CAS  PubMed  Google Scholar 

  65. Kornberg LJ. Focal adhesion kinase expression in oral cancers. Head & Neck: Journal for the Sciences and Specialties of the Head and Neck. 1998; 20(7):634-639.

    Article  CAS  Google Scholar 

  66. Judson PL, He X, Cance WG, Van Le L. Overexpression of focal adhesion kinase, a protein tyrosine kinase, in ovarian carcinoma. Cancer. 1999; 86(8):1551-1556.

    Article  CAS  PubMed  Google Scholar 

  67. Cance WG, Harris JE, Iacocca MV, et al. Immunohistochemical analyses of focal adhesion kinase expression in benign and malignant human breast and colon tissues: correlation with preinvasive and invasive phenotypes. Clinical Cancer Research. 2000; 6(6):2417-2423.

    CAS  PubMed  Google Scholar 

  68. Lark AL, Livasy CA, Calvo B, et al. Overexpression of focal adhesion kinase in primary colorectal carcinomas and colorectal liver metastases: immunohistochemistry and real-time PCR analyses. Clinical Cancer Research. 2003; 9(1):215-222.

    CAS  PubMed  Google Scholar 

  69. Zotti T, Scudiero I, Vito P, Stilo R. The emerging role of TRAF7 in tumor development. Journal of cellular physiology. 2017; 232(6):1233-1238.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Miyamoto S, Nakanishi M, Rosenberg DW. Suppression of colon carcinogenesis by targeting Notch signaling. Carcinogenesis. 2013; 34(10):2415-2423.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Akaogi K, Nakajima Y, Ito I, et al. KLF4 suppresses estrogen-dependent breast cancer growth by inhibiting the transcriptional activity of ERα. Oncogene. 2009; 28(32):2894-2902.

    Article  CAS  PubMed  Google Scholar 

  72. Riverso M, Montagnani V, Stecca B. KLF4 is regulated by RAS/RAF/MEK/ERK signaling through E2F1 and promotes melanoma cell growth. Oncogene. 2017; 36(23):3322-3333.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. von Spreckelsen N, Waldt N, Poetschke R, et al. KLF4 K409Q–mutated meningiomas show enhanced hypoxia signaling and respond to mTORC1 inhibitor treatment. Acta neuropathologica communications. 2020; 8(1):1-11.

    Google Scholar 

  74. Tang H, Zhu H, Wang X, et al. KLF4 is a tumor suppressor in anaplastic meningioma stem-like cells and human meningiomas. Journal of molecular cell biology. 2017; 9(4):315-324.

    Article  CAS  PubMed  Google Scholar 

  75. Abedalthagafi M, Bi WL, Aizer AA, et al. Oncogenic PI3K mutations are as common as AKT1 and SMO mutations in meningioma. Neuro-oncology. 2016; 18(5):649-655.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Reuss DE, Piro RM, Jones DT, et al. Secretory meningiomas are defined by combined KLF4 K409Q and TRAF7 mutations. Acta neuropathologica. 2013; 125(3):351-358.

    Article  CAS  PubMed  Google Scholar 

  77. Sahm F, Bissel J, Koelsche C, et al. AKT1E17K mutations cluster with meningothelial and transitional meningiomas and can be detected by SFRP1 immunohistochemistry. Acta neuropathologica. 2013; 126(5):757-762.

    Article  CAS  PubMed  Google Scholar 

  78. di Magliano MP, Hebrok M. Hedgehog signalling in cancer formation and maintenance. Nature reviews cancer. 2003; 3(12):903-911.

    Article  Google Scholar 

  79. Booth DR. The hedgehog signalling pathway and its role in basal cell carcinoma. Cancer and Metastasis Reviews. 1999; 18(2):261-284.

    Article  CAS  PubMed  Google Scholar 

  80. Toftgård R. Hedgehog signalling in cancer. Cellular and Molecular Life Sciences CMLS. 2000; 57(12):1720-1731.

    Article  PubMed  Google Scholar 

  81. Boetto J, Bielle F, Sanson M, Peyre M, Kalamarides M. SMO mutation status defines a distinct and frequent molecular subgroup in olfactory groove meningiomas. Neuro-oncology. 2017; 19(3):345-351.

    PubMed  PubMed Central  Google Scholar 

  82. Aavikko M, Li S-P, Saarinen S, et al. Loss of SUFU function in familial multiple meningioma. The American Journal of Human Genetics. 2012; 91(3):520-526.

    Article  CAS  PubMed  Google Scholar 

  83. Askaner G, Lei U, Bertelsen B, Venzo A, Wadt K. Novel SUFU Frameshift Variant Leading to Meningioma in Three Generations in a Family with Gorlin Syndrome. Case Reports in Genetics. 2019; 2019.

    Google Scholar 

  84. Preusser M, Brastianos PK, Mawrin C. Advances in meningioma genetics: novel therapeutic opportunities. Nature Reviews Neurology. 2018; 14(2):106-115.

    Article  CAS  PubMed  Google Scholar 

  85. Fruman DA, Chiu H, Hopkins BD, Bagrodia S, Cantley LC, Abraham RT. The PI3K pathway in human disease. Cell. 2017; 170(4):605-635.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Yang J, Nie J, Ma X, Wei Y, Peng Y, Wei X. Targeting PI3K in cancer: mechanisms and advances in clinical trials. Molecular cancer. 2019; 18(1):26.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Kang S, Bader AG, Vogt PK. Phosphatidylinositol 3-kinase mutations identified in human cancer are oncogenic. Proceedings of the National Academy of Sciences. 2005; 102(3):802-807.

    Article  CAS  Google Scholar 

  88. Lange SS, Takata K-i, Wood RD. DNA polymerases and cancer. Nature reviews cancer. 2011; 11(2):96-110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Sahm F, Schrimpf D, Stichel D, et al. DNA methylation-based classification and grading system for meningioma: a multicentre, retrospective analysis. The lancet oncology. 2017; 18(5):682-694.

    Article  CAS  PubMed  Google Scholar 

  90. Smith MJ. Germline and somatic mutations in meningiomas. Cancer genetics. 2015; 208(4):107-114.

    Article  CAS  PubMed  Google Scholar 

  91. Smith MJ, O’Sullivan J, Bhaskar SS, et al. Loss-of-function mutations in SMARCE1 cause an inherited disorder of multiple spinal meningiomas. Nature genetics. 2013; 45(3):295-298.

    Google Scholar 

  92. Roberts C, Biegel J. The role of SMARCB1/INI1 in the development of rhabdoid tumors. Cancer biology & therapy. 2009; 8(5):412-416.

    Article  CAS  Google Scholar 

  93. Hulsebos TJ, Plomp AS, Wolterman RA, Robanus-Maandag EC, Baas F, Wesseling P. Germline mutation of INI1/SMARCB1 in familial schwannomatosis. The American Journal of Human Genetics. 2007; 80(4):805-810.

    Article  CAS  PubMed  Google Scholar 

  94. Smith MJ, Wallace AJ, Bowers NL, Eaton H, Evans DGR. SMARCB1 mutations in schwannomatosis and genotype correlations with rhabdoid tumors. Cancer genetics. 2014; 207(9):373-378.

    Article  CAS  PubMed  Google Scholar 

  95. Wang AS, Jamshidi AO, Oh N, et al. Somatic SMARCB1 mutation in sporadic multiple meningiomas: case report. Frontiers in neurology. 2018; 9:919.

    Article  PubMed  PubMed Central  Google Scholar 

  96. Rieske P, Zakrzewska M, Piaskowski S, et al. Molecular heterogeneity of meningioma with INI1 mutation. Molecular Pathology. 2003; 56(5):299.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Hadfield KD, Smith MJ, Trump D, Newman WG, Evans D. SMARCB1 mutations are not a common cause of multiple meningiomas. Journal of medical genetics. 2010; 47(8):567-568.

    Article  CAS  PubMed  Google Scholar 

  98. Christiaans I, Kenter S, Brink H, et al. Germline SMARCB1 mutation and somatic NF2 mutations in familial multiple meningiomas. Journal of medical genetics. 2011; 48(2):93-97.

    Article  CAS  PubMed  Google Scholar 

  99. Sethuraman A, Brown M, Seagroves TN, Wu Z-H, Pfeffer LM, Fan M. SMARCE1 regulates metastatic potential of breast cancer cells through the HIF1A/PTK2 pathway. Breast Cancer Research. 2016; 18(1):81.

    Article  PubMed  PubMed Central  Google Scholar 

  100. Sokol ES, Feng Y-X, Jin DX, et al. SMARCE1 is required for the invasive progression of in situ cancers. Proceedings of the National Academy of Sciences. 2017; 114(16):4153-4158.

    Article  CAS  Google Scholar 

  101. Gerkes E, Fock J, den Dunnen W, et al. A heritable form of SMARCE1-related meningiomas with important implications for follow-up and family screening. Neurogenetics. 2016; 17(2):83-89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Evans LT, Van Hoff J, Hickey WF, et al. SMARCE1 mutations in pediatric clear cell meningioma: case report. Journal of Neurosurgery: Pediatrics. 2015; 16(3):296-300.

    PubMed  Google Scholar 

  103. Tauziede-Espariat A, Parfait B, Besnard A, et al. Loss of SMARCE1 expression is a specific diagnostic marker of clear cell meningioma: a comprehensive immunophenotypical and molecular analysis. Brain Pathology. 2018; 28(4):466-474.

    Article  CAS  PubMed  Google Scholar 

  104. Collord G, Tarpey P, Kurbatova N, et al. An integrated genomic analysis of anaplastic meningioma identifies prognostic molecular signatures. Scientific reports. 2018; 8(1):1-13.

    Article  CAS  Google Scholar 

  105. Harmancı AS, Youngblood MW, Clark VE, et al. Integrated genomic analyses of de novo pathways underlying atypical meningiomas. Nature communications. 2017; 8(1):1-14.

    Article  Google Scholar 

  106. Shankar GM, Santagata S. BAP1 mutations in high-grade meningioma: implications for patient care. Neuro-oncology. 2017; 19(11):1447-1456.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Perry A, Scheithauer BW, Stafford SL, Abell-Aleff PC, Meyer FB. “Rhabdoid” meningioma: an aggressive variant. The American journal of surgical pathology. 1998; 22(12):1482-1490.

    Google Scholar 

  108. Mardi K, Thakur R, Biswas B. Rhabdoid meningioma lacking malignant features: Report of a rare case with review of literature. Asian journal of neurosurgery. 2015; 10(2):172.

    Article  PubMed  PubMed Central  Google Scholar 

  109. Kim J-K, Jung T-Y, Jung S, Lee K-H, Kim S-K, Lee EJ. Meningiomas with rhabdoid or papillary components: prognosis and comparison with anaplastic meningiomas. Journal of Korean Neurosurgical Society. 2016; 59(4):357.

    Article  PubMed  PubMed Central  Google Scholar 

  110. Landry AP, Wang JZ, Nassiri F, Patil V, Gao A, Zadeh G. BAP1-deficient meningioma presenting with trabecular architecture and cytokeratin expression: a report of two cases and review of the literature. J Clin Pathol. 2021 Dec 14:jclinpath-2021-207952. https://doi.org/10.1136/jclinpath-2021-207952. Epub ahead of print. PMID: 34907091.

  111. Cheung M, Testa JR. BAP1, a tumor suppressor gene driving malignant mesothelioma. Translational Lung Cancer Research. 2017; 6(3):270.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Harbour JW, Onken MD, Roberson ED, et al. Frequent mutation of BAP1 in metastasizing uveal melanomas. Science. 2010; 330(6009):1410-1413.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Peña-Llopis S, Vega-Rubín-de-Celis S, Liao A, et al. BAP1 loss defines a new class of renal cell carcinoma. Nature genetics. 2012; 44(7):751.

    Article  PubMed  PubMed Central  Google Scholar 

  114. Horn S, Figl A, Rachakonda PS, et al. TERT promoter mutations in familial and sporadic melanoma. Science. 2013; 339(6122):959-961.

    Article  CAS  PubMed  Google Scholar 

  115. Eckel-Passow JE, Lachance DH, Molinaro AM, et al. Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. New England Journal of Medicine. 2015; 372(26):2499-2508.

    Article  CAS  PubMed  Google Scholar 

  116. Liu X, Wu G, Shan Y, Hartmann C, Von Deimling A, Xing M. Highly prevalent TERT promoter mutations in bladder cancer and glioblastoma. Cell cycle. 2013; 12(10):1637-1638.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Rachakonda PS, Hosen I, De Verdier PJ, et al. TERT promoter mutations in bladder cancer affect patient survival and disease recurrence through modification by a common polymorphism. Proceedings of the National Academy of Sciences. 2013; 110(43):17426-17431.

    Article  CAS  Google Scholar 

  118. Goutagny S, Nault JC, Mallet M, Henin D, Rossi JZ, Kalamarides M. High incidence of activating TERT promoter mutations in meningiomas undergoing malignant progression. Brain pathology. 2014; 24(2):184-189.

    Article  CAS  PubMed  Google Scholar 

  119. Abedalthagafi MS, Bi WL, Merrill PH, et al. ARID1A and TERT promoter mutations in dedifferentiated meningioma. Cancer genetics. 2015; 208(6):345-350.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Biczok A, Kraus T, Suchorska B, et al. TERT promoter mutation is associated with worse prognosis in WHO grade II and III meningiomas. Journal of neuro-oncology. 2018; 139(3):671-678.

    Article  CAS  PubMed  Google Scholar 

  121. Juratli TA, Thiede C, Koerner MV, et al. Intratumoral heterogeneity and TERT promoter mutations in progressive/higher-grade meningiomas. Oncotarget. 2017; 8(65):109228.

    Article  PubMed  PubMed Central  Google Scholar 

  122. Sahm F, Schrimpf D, Olar A, et al. TERT promoter mutations and risk of recurrence in meningioma. Journal of the National Cancer Institute. 2016; 108(5):djv377.

    Google Scholar 

  123. Spiegl-Kreinecker S, Lötsch D, Neumayer K, et al. TERT promoter mutations are associated with poor prognosis and cell immortalization in meningioma. Neuro-oncology. 2018; 20(12):1584-1593.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. De Leon AD, Cronkhite JT, Katzenstein A-LA, et al. Telomere lengths, pulmonary fibrosis and telomerase (TERT) mutations. PloS one. 2010; 5(5):e10680.

    Article  Google Scholar 

  125. Fu Z, Malureanu L, Huang J, et al. Plk1-dependent phosphorylation of FoxM1 regulates a transcriptional programme required for mitotic progression. Nat Cell Biol. 2008; 10(9):1076-1082.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Korver W, Schilham MW, Moerer P, et al. Uncoupling of S phase and mitosis in cardiomyocytes and hepatocytes lacking the winged-helix transcription factor Trident. Curr Biol. 1998; 8(24):1327-1330.

    Article  CAS  PubMed  Google Scholar 

  127. Kalinichenko VV, Major ML, Wang X, et al. Foxm1b transcription factor is essential for development of hepatocellular carcinomas and is negatively regulated by the p19ARF tumor suppressor. Genes Dev. 2004; 18(7):830-850.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Kalin TV, Wang IC, Ackerson TJ, et al. Increased levels of the FoxM1 transcription factor accelerate development and progression of prostate carcinomas in both TRAMP and LADY transgenic mice. Cancer Res. 2006; 66(3):1712-1720.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Teh MT, Wong ST, Neill GW, Ghali LR, Philpott MP, Quinn AG. FOXM1 is a downstream target of Gli1 in basal cell carcinomas. Cancer Res. 2002; 62(16):4773-4780.

    CAS  PubMed  Google Scholar 

  130. Liu M, Dai B, Kang SH, et al. FoxM1B is overexpressed in human glioblastomas and critically regulates the tumorigenicity of glioma cells. Cancer Res. 2006; 66(7):3593-3602.

    Article  CAS  PubMed  Google Scholar 

  131. Zarbalis K, Choe Y, Siegenthaler JA, Orosco LA, Pleasure SJ. Meningeal defects alter the tangential migration of cortical interneurons in Foxc1hith/hith mice. Neural Dev. 2012; 7:2.

    Article  PubMed  PubMed Central  Google Scholar 

  132. Quan M, Cui J, Xia T, et al. Merlin/NF2 Suppresses Pancreatic Tumor Growth and Metastasis by Attenuating the FOXM1-Mediated Wnt/β-Catenin Signaling. Cancer Res. 2015; 75(22):4778-4789.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Vasudevan HN, Braunstein SE, Phillips JJ, et al. Comprehensive Molecular Profiling Identifies FOXM1 as a Key Transcription Factor for Meningioma Proliferation. Cell Rep. 2018; 22(13):3672-3683.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Menke JR, Raleigh DR, Gown AM, Thomas S, Perry A, Tihan T. Somatostatin receptor 2a is a more sensitive diagnostic marker of meningioma than epithelial membrane antigen. Acta Neuropathol. 2015; 130(3):441-443.

    Article  PubMed  Google Scholar 

  135. Fèvre-Montange M, Champier J, Durand A, et al. Microarray gene expression profiling in meningiomas: differential expression according to grade or histopathological subtype. Int J Oncol. 2009; 35(6):1395-1407.

    Article  PubMed  Google Scholar 

  136. Pérez-Magán E, Rodríguez de Lope A, Ribalta T, et al. Differential expression profiling analyses identifies downregulation of 1p, 6q, and 14q genes and overexpression of 6p histone cluster 1 genes as markers of recurrence in meningiomas. Neuro Oncol. 2010; 12(12):1278-1290.

    Article  PubMed  PubMed Central  Google Scholar 

  137. Kim H, Park KJ, Ryu BK, et al. Forkhead box M1 (FOXM1) transcription factor is a key oncogenic driver of aggressive human meningioma progression. Neuropathol Appl Neurobiol. 2020; 46(2):125-141.

    Article  CAS  PubMed  Google Scholar 

  138. Blais A, Labrie Y, Pouliot F, Lachance Y, Labrie C. Structure of the gene encoding the human cyclin-dependent kinase inhibitor p18 and mutational analysis in breast cancer. Biochem Biophys Res Commun. 1998; 247(1):146-153.

    Article  CAS  PubMed  Google Scholar 

  139. Drexler HG. Review of alterations of the cyclin-dependent kinase inhibitor INK4 family genes p15, p16, p18 and p19 in human leukemia-lymphoma cells. Leukemia. 1998; 12(6):845-859.

    Article  CAS  PubMed  Google Scholar 

  140. Husemann K, Wolter M, Büschges R, Boström J, Sabel M, Reifenberger G. Identification of two distinct deleted regions on the short arm of chromosome 1 and rare mutation of the CDKN2C gene from 1p32 in oligodendroglial tumors. J Neuropathol Exp Neurol. 1999; 58(10):1041-1050.

    Article  CAS  PubMed  Google Scholar 

  141. Ichimura K, Schmidt EE, Goike HM, Collins VP. Human glioblastomas with no alterations of the CDKN2A (p16INK4A, MTS1) and CDK4 genes have frequent mutations of the retinoblastoma gene. Oncogene. 1996; 13(5):1065-1072.

    CAS  PubMed  Google Scholar 

  142. Ruas M, Peters G. The p16INK4a/CDKN2A tumor suppressor and its relatives. Biochim Biophys Acta. 1998; 1378(2):F115-177.

    CAS  PubMed  Google Scholar 

  143. Joerger AC, Fersht AR. The p53 Pathway: Origins, Inactivation in Cancer, and Emerging Therapeutic Approaches. Annu Rev Biochem. 2016; 85:375-404.

    Article  CAS  PubMed  Google Scholar 

  144. Boström J, Meyer-Puttlitz B, Wolter M, et al. Alterations of the tumor suppressor genes CDKN2A (p16(INK4a)), p14(ARF), CDKN2B (p15(INK4b)), and CDKN2C (p18(INK4c)) in atypical and anaplastic meningiomas. Am J Pathol. 2001; 159(2):661-669.

    Article  PubMed  PubMed Central  Google Scholar 

  145. Goutagny S, Yang HW, Zucman-Rossi J, et al. Genomic profiling reveals alternative genetic pathways of meningioma malignant progression dependent on the underlying NF2 status. Clin Cancer Res. 2010; 16(16):4155-4164.

    Article  CAS  PubMed  Google Scholar 

  146. Sievers P, Hielscher T, Schrimpf D, et al. CDKN2A/B homozygous deletion is associated with early recurrence in meningiomas. Acta Neuropathol. 2020; 140(3):409-413.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Wang JZ, Patil V, Liu J, Dogan H, Tabatabai G, Yefet LS, Behling F, Hoffman E, Bunda S, Yakubov R, Kaloti R, Brandner S, Gao A, Cohen-Gadol A, Barnholtz-Sloan J, Skardelly M, Tatagiba M, Raleigh DR, Sahm F, Boutros PC, Aldape K. International Consortium on Meningiomas (ICOM), Nassiri F, Zadeh G. Increased mRNA expression of CDKN2A is a transcriptomic marker of clinically aggressive meningiomas. Acta Neuropathol. 2023 Apr (In Press).

    Google Scholar 

  148. Nassiri F, Liu J, Patil V, et al. A clinically applicable integrative molecular classification of meningiomas. Nature. 2021; 597(7874):119-125.

    Article  CAS  PubMed  Google Scholar 

  149. Choudhury A, Magill ST, Eaton CD, et al. Meningioma DNA methylation groups identify biological drivers and therapeutic vulnerabilities. Nat Genet. 2022; 54(5):649-659.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Bayley JCt, Hadley CC, Harmanci AO, Harmanci AS, Klisch TJ, Patel AJ. Multiple approaches converge on three biological subtypes of meningioma and extract new insights from published studies. Sci Adv. 2022; 8(5):eabm6247.

    Google Scholar 

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Authors and Affiliations

  1. MacFeeters Hamilton Neuro-Oncology Program, Princess Margaret Cancer Centre, University Health Network and University of Toronto, Toronto, ON, Canada

    Justin Z. Wang, Farshad Nassiri & Gelareh Zadeh

  2. Division of Neurosurgery, Department of Surgery, The University of Toronto, Toronto, ON, Canada

    Justin Z. Wang, Farshad Nassiri & Gelareh Zadeh

  3. Department of Neuropathology, Otto von Guericke University Magdeburg, Magdeburg, Germany

    Christian Mawrin

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  1. Justin Z. Wang
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  2. Farshad Nassiri
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  3. Christian Mawrin
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  4. Gelareh Zadeh
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Correspondence to Gelareh Zadeh .

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Editors and Affiliations

  1. Division of Neurosurgery, Department of Surgery The University of Toronto, Toronto, ON, Canada

    Gelareh Zadeh

  2. Center of Neurosurgery, Department of General Neurosurgery University of Cologne, Cologne, Germany

    Roland Goldbrunner

  3. Department of Neurosurgery, Hopitaux Robert Schuman, Luxembourg, Luxembourg

    Boris Krischek

  4. Division of Neurosurgery, Department of SurgeryThe University of Toronto, Toronto, ON, Canada

    Farshad Nassiri

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Wang, J.Z., Nassiri, F., Mawrin, C., Zadeh, G. (2023). Genomic Landscape of Meningiomas. In: Zadeh, G., Goldbrunner, R., Krischek, B., Nassiri, F. (eds) Biological and Clinical Landscape of Meningiomas. Advances in Experimental Medicine and Biology, vol 1416. Springer, Cham. https://doi.org/10.1007/978-3-031-29750-2_11

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