title: CpG island methylation in sporadic and neurofibromatis type 2-associated schwannomas.
abstract: OBJECTIVE
  The purpose of this research was to examine the DNA methylation profile of schwannomas.
  
  
  METHODS
  We examined the DNA methylation status of 12 tumor-related genes (NF2, RB1, p14(ARF), p16(INK4a), p73, TIMP-3, MGMT, DAPK, THBS1, caspase-8, TP53, and GSTP1) in 44 sporadic and/or NF2-associated schwannomas using methylation-specific PCR.
  
  
  RESULTS
  The most frequently methylated genes were THBS1 (36%), p73 (27%), MGMT (20%), NF2 (18%), and TIMP-3 (18%). The RB1/p16INK4a gene pair displayed aberrant methylayed alleles in 15% of cases, whereas methylation was relatively rare in the other genes (<5%). Methylation was tumor specific because it was absent in two nonneoplastic nerve sheath samples and two nonneoplastic brain samples studied as controls.
  
  
  CONCLUSIONS
  Our findings indicate that aberrant methylation seems to be a mechanism for NF2 gene inactivation, considered an early step in schwannoma tumorigenesis, and as well, aberrant hypermethylation of other tumor-related genes might represent secondary events that also contribute to the development of these tumors.
authors.affiliation: Department of C. Experimental, Laboratorio Oncogenetica Molecular, Hospital Universitario La Paz, Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Gonzalez-Gomez
authors.forename: M Josefa
authors.initials: MJ
authors.lastname: Bello
authors.forename: M Eva
authors.initials: ME
authors.lastname: Alonso
authors.forename: Jesus
authors.initials: J
authors.lastname: Lomas
authors.forename: Dolores
authors.initials: D
authors.lastname: Arjona
authors.forename: Jose M de
authors.initials: JM
authors.lastname: Campos
authors.forename: Jesus
authors.initials: J
authors.lastname: Vaquero
authors.forename: Alberto
authors.initials: A
authors.lastname: Isla
authors.forename: Luis
authors.initials: L
authors.lastname: Lassaletta
authors.forename: Manuel
authors.initials: M
authors.lastname: Gutierrez
authors.forename: Jose L
authors.initials: JL
authors.lastname: Sarasa
authors.forename: Juan A
authors.initials: JA
authors.lastname: Rey
mesh_terms: D000328:Adult; D000368:Aged; D019175:DNA Methylation; D015226:Dinucleoside Phosphates / Q000378:metabolism*; D005260:Female; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009442:Neurilemmoma / Q000235:genetics*; D016518:Neurofibromatosis 2 / Q000235:genetics*; D016133:Polymerase Chain Reaction
chemical_list: D015226:Dinucleoside Phosphates; C015772:CpG dinucleotide