Altered expression of imprinted genes in Wilms tumors

  • Authors:
    • Jochen Hubertus
    • Martin Lacher
    • Marietta Rottenkolber
    • Josef Müller-Höcker
    • Michael Berger
    • Maximilian Stehr
    • Dietrich von Schweinitz
    • Roland Kappler
  • View Affiliations

  • Published online on: December 20, 2010     https://doi.org/10.3892/or.2010.1113
  • Pages: 817-823
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Overexpression of insulin-like growth factor 2 (IGF2), an imprinted gene located on chromosome 11p15, has been reported as a characteristic feature in various embryonal tumors, including Wilms tumor (WT). Recent studies specified loss of imprinting (LOI) in a differential methylated region (DMR) of the IGF2/H19 cluster or loss of heterozygosity (LOH), respectively, uniparental disomy (UPD) being responsible for this overexpression. However, the role of other imprinted genes in the genesis of WT is still unknown. In the current study, we analyzed transcriptional activity of the imprinted genes IGF2, H19, NNAT, DLK1, RTL1, MEG3, and MEST as well as the methylation status of the DMR of the IGF2/H19 cluster in a panel of 32 WTs. Except for H19, we detected massive overexpression of all genes in the majority of WTs compared to normal renal tissue, which was most prominent for the paternally expressed genes IGF2, NNAT, and MEST. Alterations of the H19DMR were found in two-thirds of the WTs. Moreover, we have seen a strong correlation between the transcriptional activity of IGF2, NNAT and MEST and LOI/LOH of H19DMR, which was inverse for H19. Expression of DLK1, RTL1 and MEG3 does not correlate with LOI/LOH of H19DMR. Altogether, our findings suggest that over-expression of imprinted genes is common in WTs and correlates at least for some imprinted genes with LOI of H19DMR. Thus, it may be speculated that alterations of the DNA modification machinery drive erroneous setting of methylation marks in imprinting regions throughout the genome, which leads to the concomitant activation of imprinted genes in blastomagenesis.

Related Articles

Journal Cover

March 2011
Volume 25 Issue 3

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

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Hubertus J, Lacher M, Rottenkolber M, Müller-Höcker J, Berger M, Stehr M, von Schweinitz D and Kappler R: Altered expression of imprinted genes in Wilms tumors. Oncol Rep 25: 817-823, 2011.
APA
Hubertus, J., Lacher, M., Rottenkolber, M., Müller-Höcker, J., Berger, M., Stehr, M. ... Kappler, R. (2011). Altered expression of imprinted genes in Wilms tumors. Oncology Reports, 25, 817-823. https://doi.org/10.3892/or.2010.1113
MLA
Hubertus, J., Lacher, M., Rottenkolber, M., Müller-Höcker, J., Berger, M., Stehr, M., von Schweinitz, D., Kappler, R."Altered expression of imprinted genes in Wilms tumors". Oncology Reports 25.3 (2011): 817-823.
Chicago
Hubertus, J., Lacher, M., Rottenkolber, M., Müller-Höcker, J., Berger, M., Stehr, M., von Schweinitz, D., Kappler, R."Altered expression of imprinted genes in Wilms tumors". Oncology Reports 25, no. 3 (2011): 817-823. https://doi.org/10.3892/or.2010.1113