Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO. Academic Article uri icon

Overview

MeSH

  • Adult
  • Aged
  • Aged, 80 and over
  • Chromosomes, Human, Pair 22
  • DNA Mutational Analysis
  • Female
  • Genes, Neurofibromatosis 2
  • Genomic Instability
  • Genomics
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Grading
  • Smoothened Receptor

MeSH Major

  • Brain Neoplasms
  • Kruppel-Like Transcription Factors
  • Meningeal Neoplasms
  • Meningioma
  • Proto-Oncogene Proteins c-akt
  • Receptors, G-Protein-Coupled
  • Tumor Necrosis Factor Receptor-Associated Peptides and Proteins

abstract

  • We report genomic analysis of 300 meningiomas, the most common primary brain tumors, leading to the discovery of mutations in TRAF7, a proapoptotic E3 ubiquitin ligase, in nearly one-fourth of all meningiomas. Mutations in TRAF7 commonly occurred with a recurrent mutation (K409Q) in KLF4, a transcription factor known for its role in inducing pluripotency, or with AKT1(E17K), a mutation known to activate the PI3K pathway. SMO mutations, which activate Hedgehog signaling, were identified in ~5% of non-NF2 mutant meningiomas. These non-NF2 meningiomas were clinically distinctive-nearly always benign, with chromosomal stability, and originating from the medial skull base. In contrast, meningiomas with mutant NF2 and/or chromosome 22 loss were more likely to be atypical, showing genomic instability, and localizing to the cerebral and cerebellar hemispheres. Collectively, these findings identify distinct meningioma subtypes, suggesting avenues for targeted therapeutics.

authors

publication date

  • March 1, 2013

has subject area

  • Adult
  • Aged
  • Aged, 80 and over
  • Brain Neoplasms
  • Chromosomes, Human, Pair 22
  • DNA Mutational Analysis
  • Female
  • Genes, Neurofibromatosis 2
  • Genomic Instability
  • Genomics
  • Humans
  • Kruppel-Like Transcription Factors
  • Male
  • Meningeal Neoplasms
  • Meningioma
  • Middle Aged
  • Mutation
  • Neoplasm Grading
  • Proto-Oncogene Proteins c-akt
  • Receptors, G-Protein-Coupled
  • Smoothened Receptor
  • Tumor Necrosis Factor Receptor-Associated Peptides and Proteins

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4808587

Digital Object Identifier (DOI)

  • 10.1126/science.1233009

PubMed ID

  • 23348505

Additional Document Info

start page

  • 1077

end page

  • 1080

volume

  • 339

number

  • 6123