title: Aberrant demethylation and expression of MAGEB2 in a subset of malignant peripheral nerve sheath tumors from neurofibromatosis type 1.
abstract: BACKGROUND
  Malignant peripheral nerve sheath tumors (MPNSTs) occur in several percent of neurofibromatosis type 1 (NF-1) patients. When a CpG island (CGI) in the 5' region of a gene is methylated, transcription of that gene may be suppressed. Although cancer-testis antigens, including MAGEB2, are potential therapeutic targets for cancer in medical practice, information on MAGEB2 in MPNST is scarce.
  
  
  OBJECTIVE
  The purpose is to clarify the methylation status and expression of MAGEB2 in MPNSTs derived from patients with NF-1.
  
  
  METHODS
  Quantitative real-time methylation-specific PCR (RT-MSP) and quantitative real-time reverse transcription-PCR (RT-PCR) were performed to measure methylation and mRNA expression, respectively, in MPNST cell lines and in MPNST and neurofibroma samples from patients with NF-1. Immunohistochemical analysis was also performed to assess MAGEB2 protein expression.
  
  
  RESULTS
  RT-MSP and RT-PCR data showed low methylation levels and detectable mRNA expression of MAGEB2, respectively, in one MPNST cell line, but high methylation level and absence of expression in each other cell line and in normal cells. Based on RT-MSP data, 3 of 18 MPNST clinical samples exhibited low methylation levels; in contrast, all cutaneous and plexiform neurofibroma samples and normal cells exhibited high methylation levels. Methylation levels were not significantly associated with any clinical parameters. Immunohistochemical analysis revealed expression of MAGEB2 protein in MPNST clinical samples with the low methylation level.
  
  
  CONCLUSIONS
  MAGEB2 can be aberrantly demethylated and expressed in MPNSTs. Conversely, the gene may not be demethylated in any types of neurofibroma, suggesting that the demethylation does not occur before malignant transformation.
authors.affiliation: Department of Dermatology, The Jikei University School of Medicine, 25-8 Nishi-Shimbashi 3-chome, Minato-ku, Tokyo, Japan. Electronic address: nobederm@jikei.ac.jp.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Nobeyama
authors.affiliation: Department of Dermatology, The Jikei University School of Medicine, 25-8 Nishi-Shimbashi 3-chome, Minato-ku, Tokyo, Japan.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Nakagawa
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009456:Neurofibromatosis 1 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C072012:MAGEB2 protein, human; D009363:Neoplasm Proteins; D012333:RNA, Messenger
keywords: DNA demethylation; DNA methylation; MAGEB2; Malignant peripheral nerve sheath tumor; Neurofibromatosis type 1