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A PDGFRA promoter polymorphism, which disrupts the binding of ZNF148, is associated with primitive neuroectodermal tumours and ependymomas
  1. C De Bustos1,
  2. A Smits2,
  3. B Strömberg3,
  4. V P Collins4,
  5. M Nistér1,5,
  6. G Afink1,5
  1. 1Department of Genetics and Pathology, Uppsala University, Rudbeck Laboratory, 751 85 Uppsala, Sweden
  2. 2Department of Neuroscience, Neurology, Uppsala University, University Hospital, 751 85 Uppsala, Sweden
  3. 3Department of Women and Child Health, Uppsala University, University Children’s Hospital, 751 85 Uppsala, Sweden
  4. 4Department of Pathology, University of Cambridge, Addenbrooke’s Hospital, Cambridge CB2 QQ, UK
  5. 5Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, R8:05 Karolinska Hospital, 17176 Stockholm, Sweden
  1. Correspondence to:
 Gijs Afink
 Department of Oncology-Pathology, Karolinska Institutet, CCK R8:05 KS, 17176 Stockholm, Sweden;


Background: Platelet derived growth factor receptor α (PDGFRα) expression is typical for a variety of brain tumours, while in normal adult brain PDGFRα expression is limited to a small number of neural progenitor cells. The molecular mechanisms responsible for the PDGFRα expression in tumours are not known, but in the absence of amplification, changes in transcriptional regulation might be an important factor in this process.

Methods and results: We have investigated the link between single nucleotide polymorphisms (SNPs) within the PDGFRα 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 H2α–δ. 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 H2δ haplotype. The precise functional role in PDGFRα gene transcription for the H2δ haplotype is not known yet, but we can show that the H2δ haplotype specifically disrupts binding of the transcription factor ZNF148 as compared to the other promoter haplotypes.

Conclusions: The specific over-representation of the H2δ haplotype in both patients with PNETs and ependymomas suggests a functional role for the ZNF148/PDGFRα pathway in the pathogenesis of these tumours.

  • EMSA, electrophoretic mobility shift assay
  • PDGFR, platelet derived growth factor receptor
  • PNET, primitive neuroectodermal tumour
  • SNP, single nucleotide polymorphism
  • brain
  • cancer
  • platelet derived growth factor
  • single nucleotide polymorphism
  • transcription

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  • This work was supported by the Swedish Children’s Cancer Foundation (GA and MN); the Karolinska Institute Research Fund (GA); the James S. McDonnell Foundation, the Stockholm Cancer Society, and the Juvenile Diabetes Research Foundation (MN); the Samantha Dickson Research Trust, the Carly Watson Ependymoma Fund, Cancer Research UK, and the Jacqueline Seroussi Memorial Foundation for Cancer Research (VPC). CDB is supported by a fellowship from the Department of Education, Universities and Research of the Basque Government.

  • Competing interests: none declared