Frequent hypermethylation of a CTCF binding site influences Wilms tumor 1 expression in Wilms tumors

  • Authors:
    • Ferdinand Zitzmann
    • Doris Mayr
    • Michael Berger
    • Maximilian Stehr
    • Dietrich von Schweinitz
    • Roland Kappler
    • Jochen Hubertus
  • View Affiliations

  • Published online on: February 11, 2014     https://doi.org/10.3892/or.2014.3019
  • Pages: 1871-1876
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Abstract

The Wilms tumor 1 (WT1) gene plays an essential role in early development and differentiation of the urinary tract, particularly the kidneys. Aberrant transcriptional activity of WT1 is a key finding in the genesis of Wilms tumors (WTs). However, the mechanisms responsible for this alteration remain poorly understood. In the present study, we examined the methylation pattern of a putative CCCTC-binding factor (CTCF) binding site downstream of the WT1 gene as a potential cause of WT1 misregulation in 44 native WT specimens. We found that 16 WT cases exhibited a much higher WT1 expression compared to normal kidney tissue, and that the high mRNA expression of WT1 is strongly correlated with a high degree of DNA methylation of the CTCF binding site near the WT1 promoter. However, there was no correlation between the KTS+/KTS- splicing variants of WT1 and the methylation status of the CpGs of the CTCF binding site. Our results demonstrated an aberrant methylation pattern at a CTCF binding site downstream the WT1 gene, which is associated with an elevated WT1 transcriptional activity. Thus, methylation of the CTCF binding site may be partially responsible for the transcriptional activation of the WT1 locus and hypermethylation of this site may be an important oncogenic mechanism in the genesis of WT.
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2014-April
Volume 31 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Zitzmann F, Mayr D, Berger M, Stehr M, von Schweinitz D, Kappler R and Hubertus J: Frequent hypermethylation of a CTCF binding site influences Wilms tumor 1 expression in Wilms tumors. Oncol Rep 31: 1871-1876, 2014
APA
Zitzmann, F., Mayr, D., Berger, M., Stehr, M., von Schweinitz, D., Kappler, R., & Hubertus, J. (2014). Frequent hypermethylation of a CTCF binding site influences Wilms tumor 1 expression in Wilms tumors. Oncology Reports, 31, 1871-1876. https://doi.org/10.3892/or.2014.3019
MLA
Zitzmann, F., Mayr, D., Berger, M., Stehr, M., von Schweinitz, D., Kappler, R., Hubertus, J."Frequent hypermethylation of a CTCF binding site influences Wilms tumor 1 expression in Wilms tumors". Oncology Reports 31.4 (2014): 1871-1876.
Chicago
Zitzmann, F., Mayr, D., Berger, M., Stehr, M., von Schweinitz, D., Kappler, R., Hubertus, J."Frequent hypermethylation of a CTCF binding site influences Wilms tumor 1 expression in Wilms tumors". Oncology Reports 31, no. 4 (2014): 1871-1876. https://doi.org/10.3892/or.2014.3019