Genetic landscape of meningioma.
Meningioma is the most common intracranial tumor, arising from arachnoid cells of the meninges. Monosomy 22 and inactivating mutations of NF2 are well-known genetic alterations of meningiomas. More recently, mutations in TRAF7, AKT1, KLF4, SMO, and PIK3CA were identified by next-generation sequencing. We here reviewed 553 meningiomas for the mutational patterns of the six genes. NF2 aberration was observed in 55 % of meningiomas. Mutations of TRAF7, AKT1, KLF4, PIK3CA, and SMO were identified in 20, 9, 9, 4.5, and 3 % of cases, respectively. Altogether, 80 % of cases harbored at least one of the genetic alterations in these genes. NF2 alterations and mutations of the other genes were mutually exclusive with a few exceptions. Clinicopathologically, tumors with mutations in TRAF7/AKT1 and SMO shared specific features: they were located in the anterior fossa, median middle fossa, or anterior calvarium, and most of them were meningothelial or transitional meningiomas. TRAF7/KLF4 type meningiomas showed different characteristics in that they occurred in the lateral middle fossa and median posterior fossa as well as anterior fossa and median middle fossa, and contained a secretory meningioma component. We also discuss the mutational hotspots of these genes and other genetic/cytogenetic alterations contributing to tumorigenesis or progression of meningiomas.
Department of Diagnostic Pathology, Asahikawa Medical University, 2-1-1-1 Midorigaoka Higashi, Asahikawa, Hokkaido, 078-8510, Japan. ysayaka528@asahikawa-med.ac.jp.|Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. ysayaka528@asahikawa-med.ac.jp.
Sayaka
http://orcid.org/0000-0002-2337-4000
S
Yuzawa
Department of Translational Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.|Translational Research Laboratory, Hokkaido University Hospital, Clinical Research and Medical Innovation Center, Sapporo, Japan.
Hiroshi
H
Nishihara
Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.|Department of Translational Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Shinya
S
Tanaka
D025063:Chromosome Disorders; D002892:Chromosomes, Human, Pair 22; D058534:Class I Phosphatidylinositol 3-Kinases; D018450:Disease Progression; D056726:Genetic Association Studies; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D008577:Meningeal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008579:Meningioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009030:Mosaicism; D009154:Mutation; D025581:Neurofibromin 2 / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D019291:Skull Base / Q000378:metabolism; D000072086:Smoothened Receptor / Q000235:genetics / Q000378:metabolism; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000235:genetics / Q000378:metabolism
D058534:Class I Phosphatidylinositol 3-Kinases; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D025581:Neurofibromin 2; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D000072086:Smoothened Receptor; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; C000715467:KLF4 protein, human; C491023:SMO protein, human; C486460:TRAF7 protein, human; C484760:PIK3CA protein, human; C494918:AKT1 protein, human
Genetics; Meningioma; Next-generation sequencers