title: Genomic and transcriptome analysis revealing an oncogenic functional module in meningiomas.
abstract: OBJECTIVE
  Meningiomas are among the most common primary adult brain tumors. Although typically benign, roughly 2%-5% display malignant pathological features. The key molecular pathways involved in malignant transformation remain to be determined.
  
  
  METHODS
  Illumina expression microarrays were used to assess gene expression levels, and Illumina single-nucleotide polymorphism arrays were used to identify copy number variants in benign, atypical, and malignant meningiomas (19 tumors, including 4 malignant ones). The authors also reanalyzed 2 expression data sets generated on Affymetrix microarrays (n = 68, including 6 malignant ones; n = 56, including 3 malignant ones). A weighted gene coexpression network approach was used to identify coexpression modules associated with malignancy.
  
  
  RESULTS
  At the genomic level, malignant meningiomas had more chromosomal losses than atypical and benign meningiomas, with average length of 528, 203, and 34 megabases, respectively. Monosomic loss of chromosome 22 was confirmed to be one of the primary chromosomal level abnormalities in all subtypes of meningiomas. At the transcriptome level, the authors identified 23 coexpression modules from the weighted gene coexpression network. Gene functional enrichment analysis highlighted a module with 356 genes that was highly related to tumorigenesis. Four intramodular hubs within the module (GAB2, KLF2, ID1, and CTF1) were oncogenic in other cancers such as leukemia. A putative meningioma tumor suppressor MN1 was also identified in this module with differential expression between malignant and benign meningiomas.
  
  
  CONCLUSIONS
  The authors' genomic and transcriptome analysis of meningiomas provides novel insights into the molecular pathways involved in malignant transformation of meningiomas, with implications for molecular heterogeneity of the disease.
authors.affiliation: Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California;
authors.forename: Xiao
authors.initials: X
authors.lastname: Chang
authors.forename: Lingling
authors.initials: L
authors.lastname: Shi
authors.forename: Fan
authors.initials: F
authors.lastname: Gao
authors.forename: Jonathan
authors.initials: J
authors.lastname: Russin
authors.forename: Liyun
authors.initials: L
authors.lastname: Zeng
authors.forename: Shuhan
authors.initials: S
authors.lastname: He
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Chen
authors.forename: Steven L
authors.initials: SL
authors.lastname: Giannotta
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weisenberger
authors.forename: Gabriel
authors.initials: G
authors.lastname: Zada
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: William J
authors.initials: WJ
authors.lastname: Mack
mesh_terms: D063646:Carcinogenesis / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D018628:Gene Dosage; D015870:Gene Expression / Q000235:genetics; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks / Q000235:genetics; D023281:Genomics; D006801:Humans; D008577:Meningeal Neoplasms / Q000235:genetics* / Q000378:metabolism; D008579:Meningioma / Q000235:genetics* / Q000378:metabolism