Genetic landscape of meningioma

• Published in: Brain tumor pathology Vol. 33; no. 4; pp. 237 - 247
• Main Authors: Yuzawa, Sayaka, Nishihara, Hiroshi, Tanaka, Shinya
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01-10-2016; Springer Nature B.V
• Subjects: Brain cancer; Cancer Research; Chromosome Disorders; Chromosomes; Chromosomes, Human, Pair 22; Class I Phosphatidylinositol 3-Kinases; Disease Progression; Genes; Genetic Association Studies; Humans; Kinases; Kruppel-Like Transcription Factors - genetics; Kruppel-Like Transcription Factors - metabolism; Medicine; Medicine & Public Health; Meningeal Neoplasms - genetics; Meningeal Neoplasms - metabolism; Meningeal Neoplasms - pathology; Meningioma - genetics; Meningioma - metabolism; Meningioma - pathology; Mosaicism; Mutation; Neurofibromin 2 - genetics; Neurofibromin 2 - metabolism; Neurology; Neurosurgery; Oncology; Pathology; Phosphatidylinositol 3-Kinases - genetics; Phosphatidylinositol 3-Kinases - metabolism; Proteins; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Review Article; Skull Base - metabolism; Smoothened Receptor - genetics; Smoothened Receptor - metabolism; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins - genetics; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins - metabolism; Tumors; Genetics; Meningioma; Next-generation sequencers
• DOI: 10.1007/s10014-016-0271-7
• EISSN: 1861-387X
• ISSN: 1433-7398

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.