title: The role of the WNT/β-catenin pathway in central nervous system primitive neuroectodermal tumours (CNS PNETs).
abstract: BACKGROUND
  Central nervous system primitive neuroectodermal tumours (CNS PNETs) are embryonal tumours occurring predominantly in children. Current lack of knowledge regarding their underlying biology hinders development of more effective treatments. We previously identified WNT/β-catenin pathway activation in one-third of CNS PNETs, which was potentially linked to a better prognosis. In this study, we have extended our cohort, achieving a statistically significant correlation with prognosis. We additionally investigated the biological effects of WNT/β-catenin pathway activation in tumour pathogenesis.
  
  
  METHODS
  A total of 42 primary and 8 recurrent CNS PNETs were analysed for WNT/β-catenin pathway status using β-catenin immunohistochemistry. Genomic copy number and mRNA expression data were analysed to identify a molecular profile linked to WNT/β-catenin pathway activation.
  
  
  RESULTS
  Pathway activation was seen in 26% of CNS PNETs and was significantly associated with longer overall survival. Genes displaying a significant difference in expression levels, between tumours with and without WNT/β-catenin pathway activation, included several involved in normal CNS development suggesting aberrant pathway activation may be disrupting this process.
  
  
  CONCLUSIONS
  We have identified WNT/β-catenin pathway status as a marker, which could potentially be used to stratify disease risk for patients with CNS PNET. Gene expression data suggest pathway activation is disrupting normal differentiation in the CNS.
authors.affiliation: Children's Brain Tumour Research Centre, Department of Clinical Sciences, D Floor Medical School, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK. hazel.rogers@nottingham.ac.uk
authors.forename: H A
authors.initials: HA
authors.lastname: Rogers
authors.forename: J H
authors.initials: JH
authors.lastname: Ward
authors.forename: S
authors.initials: S
authors.lastname: Miller
authors.forename: J
authors.initials: J
authors.lastname: Lowe
authors.forename: B
authors.initials: B
authors.lastname: Coyle
authors.forename: R G
authors.initials: RG
authors.lastname: Grundy
mesh_terms: D016543:Central Nervous System Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D002648:Child; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D046228:Microarray Analysis; D018242:Neuroectodermal Tumors, Primitive / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D012189:Retrospective Studies; D016019:Survival Analysis; D059467:Transcriptome; D014407:Tumor Cells, Cultured; D060449:Wnt Signaling Pathway / Q000235:genetics / Q000502:physiology*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D051176:beta Catenin