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Open Access 01-12-2014 | Research article

Epigenetic silencing of genes and microRNAs within the imprinted Dlk1-Dio3 region at human chromosome 14.32 in giant cell tumor of bone

Authors: Burkhard Lehner, Pierre Kunz, Heiner Saehr, Joerg Fellenberg

Published in: BMC Cancer | Issue 1/2014

Abstract

Background

Growing evidence exists that the neoplastic stromal cell population (GCTSC) within giant cell tumors (GCT) originates from mesenchymal stem cells (MSC). In a previous study we identified a microRNA signature that differentiates between these cell types. Five differentially expressed microRNAs are located within the Dlk1-Dio3 region on chromosome 14. Aberrant regulation within this region is known to influence cell growth, differentiation and the development of cancer. The aim of this study was to elucidate the involvement of deregulations within the Dlk1-Dio3 region in GCT pathogenesis.

Methods

Quantitative gene and microRNA expression analyses were performed on GCTSCs and MSCs with or without treatment with epigenetic modifiers. Methylation analysis of differentially methylated regions was performed by bisulfite sequencing.

Results

In addition to microRNA silencing we detected a significant downregulation of Dlk1, Meg3 and Meg8 in GCTSCs compared to MSCs. DNA methylation analyses of the Meg3-DMR and IG-DMR revealed a frequent hypermethylation within the IG-DMR in GCTs. Epigenetic modification could restore expression of some but not all analyzed genes and microRNAs suggesting further regulatory mechanisms.

Conclusion

Epigenetic silencing of genes and microRNAs within the Dlk1-Dio3 region is a common event in GCTSCs, in part mediated by hypermethylation within the IG-DMR. The identified genes, micro RNAs and microRNA target genes might be valuable targets for the development of improved strategies for GCT diagnosis and therapy.

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The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/14/495/prepub

Title: Epigenetic silencing of genes and microRNAs within the imprinted Dlk1-Dio3 region at human chromosome 14.32 in giant cell tumor of bone
Authors: Burkhard Lehner
Pierre Kunz
Heiner Saehr
Joerg Fellenberg
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/1471-2407-14-495

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