PT  - JOURNAL ARTICLE
AU  - De Bustos, C
AU  - Smits, A
AU  - Strömberg, B
AU  - Collins, V P
AU  - Nistér, M
AU  - Afink, G
TI  - A <em>PDGFRA</em> promoter polymorphism, which disrupts the binding of ZNF148, is associated with primitive neuroectodermal tumours and ependymomas
AID  - 10.1136/jmg.2004.024034
DP  - 2005 Jan 01
TA  - Journal of Medical Genetics
PG  - 31--37
VI  - 42
IP  - 1
4099  - http://jmg.bmj.com/content/42/1/31.short
4100  - http://jmg.bmj.com/content/42/1/31.full
SO  - J Med Genet2005 Jan 01; 42
AB  - 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.