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- W2016355549 abstract "Aberrant expression of the platelet-derived growth factor α-receptor (PDGFRA) gene has been associated with various diseases, including neural tube defects and gliomas. We have previously identified 5 distinct haplotypes for the PDGFRA promoter region, designated H1, H2α, H2β, H2γ and H2δ. Of these haplotypes H1 and H2α are the most common, whereby H1 drives low and H2α high transcriptional activity in transient transfection assays. Here we have investigated the role of these PDGFRA promoter haplotypes in gliomagenesis at both the genetic and cellular level. In a case–control study on 71 glioblastoma patients, we observed a clear underrepresentation of H1 alleles, with pH1 = 0.141 in patients and pH1 = 0.211 in a combined Western European control group (n = 998, p < 0.05). Furthermore, in 3 out of 4 available H1/H2α heterozygous human glioblastoma cell lines, H1-derived mRNA levels were more than 10-fold lower than from H2α, resulting at least in part from haplotype-specific epigenetic differences such as DNA methylation and histone acetylation. Together, these results indicate that PDGFRA promoter haplotypes may predispose to gliomas. We propose a model in which PDGFRA is upregulated in a haplotype-specific manner during neural stem cell differentiation, which affects the pool size of cells that can later undergo gliomagenesis. © 2008 Wiley-Liss, Inc." @default.
- W2016355549 created "2016-06-24" @default.
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- W2016355549 date "2008-05-07" @default.
- W2016355549 modified "2023-10-18" @default.
- W2016355549 title "Haplotype-specific expression of the human PDGFRA gene correlates with the risk of glioblastomas" @default.
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- W2016355549 doi "https://doi.org/10.1002/ijc.23432" @default.
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