title: Identification of the deleted in liver cancer 1 gene, DLC1, as a candidate meningioma tumor suppressor.
abstract: OBJECTIVE
  Meningiomas are the second most common primary tumors of the central nervous system. Meningiomas at the cranial base pose technical challenges and result in increased morbidity. To investigate the molecular mechanisms of meningioma formation, the expression profiles of 12 000 genes from meningiomas and dural specimens were compared.
  
  
  METHODS
  Ribonucleic acid from 6 meningiomas (World Health Organization Grade I) and 4 dural specimens was profiled using U95A GeneChips (Affymetrix, Inc., Santa Clara, CA). Expression profiles of the 2 groups were compared using dChip and Data Mining Tool software packages (Affymetrix, Inc.) to identify differentially expressed genes. Down-regulation of a differentially expressed tumor suppressor gene, deleted in liver cancer 1 (DLC1), was verified by quantitative real-time reverse transcription-polymerase chain reaction and immunohistochemical staining. Function and methylation of DLC1 were assessed by ectopic expression in 5 primary cultures, demethylation assay using 5-aza-2'-deoxycytidine, and methylation-specific polymerase chain reaction in 4 meningioma samples.
  
  
  RESULTS
  Gene expression profiling revealed up-regulation of 5 genes (fibroblast growth factor 9, gibbon leukemia virus receptor 2, cyclin D1, eukaryotic translation initiation factor 5A, and 28S ribosomal ribonucleic acid) and down-regulation of 35 genes, including DLC1, in meningiomas. The down-regulation of DLC1 in meningiomas was confirmed by quantitative real-time reverse transcription-polymerase chain reaction and immunohistochemical staining. Transfection of DLC1 complementary deoxyribonucleic acid into primary cultures of 5 meningiomas resulted in decreased replication. Although demethylation decreased meningioma cell growth rates in vitro, methylation-specific polymerase chain reaction did not detect DLC1 promoter methylation.
  
  
  CONCLUSIONS
  The results suggest that DLC1 may function as a tumor suppressor gene in meningiomas. Furthermore, DLC1 promoter methylation does not appear to be responsible for the decreased DLC1 expression in these tumors.
authors.affiliation: Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Gerald R
authors.initials: GR
authors.lastname: Hankins
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Sasaki
authors.forename: Ann-Shung
authors.initials: AS
authors.lastname: Lieu
authors.forename: Dwight
authors.initials: D
authors.lastname: Saulle
authors.forename: Kambiz
authors.initials: K
authors.lastname: Karimi
authors.forename: Jin Zhong
authors.initials: JZ
authors.lastname: Li
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Helm
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D049109:Cell Proliferation; D019175:DNA Methylation / Q000235:genetics; D015536:Down-Regulation; D004388:Dura Mater / Q000378:metabolism; D005260:Female; D020690:GTPase-Activating Proteins; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D008297:Male; D008579:Meningioma / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C112352:DLC1 protein, human; D020690:GTPase-Activating Proteins; D025521:Tumor Suppressor Proteins