title: A PDGFRA promoter polymorphism, which disrupts the binding of ZNF148, is associated with primitive neuroectodermal tumours and ependymomas.
abstract: BACKGROUND
  Platelet derived growth factor receptor alpha (PDGFRalpha) expression is typical for a variety of brain tumours, while in normal adult brain PDGFRalpha expression is limited to a small number of neural progenitor cells. The molecular mechanisms responsible for the PDGFRalpha expression in tumours are not known, but in the absence of amplification, changes in transcriptional regulation might be an important factor in this process.
  
  
  RESULTS
  We have investigated the link between single nucleotide polymorphisms (SNPs) within the PDGFRalpha gene promoter and the occurrence of brain tumours (medulloblastomas, supratentorial primitive neuroectodermal tumours (PNETs), ependymal tumours, astrocytomas, oligodendrogliomas, and mixed gliomas). These SNPs give rise to five different promoter haplotypes named H1 and H2alpha-delta. It is apparent from the haplotype frequency distribution that both PNET (10-fold) and ependymoma (6.5-fold) patient groups display a significant over-representation of the H2delta haplotype. The precise functional role in PDGFRalpha gene transcription for the H2delta haplotype is not known yet, but we can show that the H2delta haplotype specifically disrupts binding of the transcription factor ZNF148 as compared to the other promoter haplotypes.
  
  
  CONCLUSIONS
  The specific over-representation of the H2delta haplotype in both patients with PNETs and ependymomas suggests a functional role for the ZNF148/PDGFRalpha pathway in the pathogenesis of these tumours.
authors.affiliation: Department of Genetics and Pathology, Uppsala University, Rudbeck Laboratory, 751 85 Uppsala, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: De Bustos
authors.forename: A
authors.initials: A
authors.lastname: Smits
authors.forename: B
authors.initials: B
authors.lastname: Strömberg
authors.forename: V P
authors.initials: VP
authors.lastname: Collins
authors.forename: M
authors.initials: M
authors.lastname: Nistér
authors.forename: G
authors.initials: G
authors.lastname: Afink
mesh_terms: D001483:Base Sequence; D001932:Brain Neoplasms / Q000145:classification / Q000235:genetics*; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004806:Ependymoma / Q000235:genetics*; D006801:Humans; D017599:Neuroectodermal Tumors / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics* / Q000378:metabolism*; D012016:Reference Values; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C110951:ZNF148 protein, human; D020796:Receptor, Platelet-Derived Growth Factor alpha