title: [Risk stratification in medulloblastoma: screening for molecular markers].
abstract: BACKGROUND
  The present study evaluates molecular markers for patients at risk of poor or no response to medulloblastoma. The aim of the study is to optimize therapy stratification.
  
  
  METHODS
  69 snap-frozen medulloblastoma samples were examined. C-MYC amplification was determined by fluorescence in situ hybridisation (FISH) analysis. Methylation specific PCR revealed the level of promoter methylation status of the tumor suppressor genes CASP8 (Caspase 8), TIMP3, CDH1 (E-Cadherin), CDKN2A (p16) and MGMT. Expression of GAS7 was evaluated by RT-PCR.
  
  
  RESULTS
  C-MYC amplification: 4/69 tumors displayed high level amplification; 53/69 tumors displayed low level (< 4 copies) or no amplification; 12/69 samples were not predictive. In patients with c-MYC amplification a tendency towards unfavorable outcome was observed (p = 0.3). Promoter methylation status: CASP8: in 36/40 tumors methylated; TIMP3: 1/38 methylated; MGMT 0/44 methylated; CDKN2A: 1/46 methylated; E-cadherin 3/36 methylated; no association between methylation status and clinical outcome. GAS7: Detection of specific RNA in 20/29 medulloblastoma samples.
  
  
  CONCLUSIONS
  No significant association between amplification of c-MYC and clinical outcome was observed. Promoter methylation of tumor suppressor genes is non-randomly distributed with a high level of methylation of CASP8. Recent studies show that silencing of CASP8 by methylation could be overcome by interferon gamma providing a possible therapeutic mechanism. GAS7 was shown to be a marker of mature neuronal cells with potential antitumorigenic capacity in neuronal tumors. In medulloblastoma 20/29 of the tumors examined express GAS7. Therefore a tumor suppressing function of GAS7 is improbable.
authors: Abteilung für Molekulare Pathologie, Institut für Pathologie, Universitätsklinikum Tübingen.
authors: M
authors: M
authors: Ebinger
authors: L
authors: L
authors: Senf
authors: W
authors: W
authors: Scheurlen