Oncotarget

Research Papers: Gerotarget (Focus on Aging):

DNA methylation in PRDM8 is indicative for dyskeratosis congenita

Carola I. Weidner, Qiong Lin, Carina Birkhofer, Uwe Gerstenmaier, Andrea Kaifie, Martin Kirschner, Heiko Bruns, Stefan Balabanov, Arne Trummer, Clemens Stockklausner, Britta Höchsmann, Hubert Schrezenmeier, Marcin Wlodarski, Jens Panse, Tim H. Brümmendorf, Fabian Beier and Wolfgang Wagner _

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Oncotarget. 2016; 7:10765-10772. https://doi.org/10.18632/oncotarget.7458

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Abstract

Carola I. Weidner1,2, Qiong Lin1,2, Carina Birkhofer3, Uwe Gerstenmaier3, Andrea Kaifie4, Martin Kirschner4, Heiko Bruns5, Stefan Balabanov6, Arne Trummer7, Clemens Stockklausner8, Britta Höchsmann9,10, Hubert Schrezenmeier9,10, Marcin Wlodarski11, Jens Panse4, Tim H. Brümmendorf4, Fabian Beier4,* and Wolfgang Wagner1,2,*

1 Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University Medical Faculty, Aachen, Germany

2 Institute for Biomedical Technology – Cell Biology, RWTH University Medical School, Aachen, Germany

3 Varionostic GmbH, Ulm, Germany

4 Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, RWTH Aachen University Medical Faculty, Aachen, Germany

5 Department of Internal Medicine 5-Hematology/Oncology, University Hospital Erlangen, Erlangen, Germany

6 Division of Hematology, University Hospital Zurich, Zurich, Switzerland

7 Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany

8 Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany

9 Institute of Transfusion Medicine, University of Ulm, Ulm, Germany

10 Institute of Clinical Transfusion Medicine and Immunogenetics, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University Hospital Ulm, Ulm, Germany

11 Department of Pediatrics, Hematology and Oncology, University of Freiburg, Freiburg, Germany

* These authors have contributed equally to this work

Correspondence to:

Wolfgang Wagner, email:

Fabian Beier, email:

Keywords: aplastic anemia, bone marrow failure, DNA methylation, dyskeratosis congenita, epigenetic, Gerotarget

Received: January 20, 2016 Accepted: February 09, 2016 Published: February 17, 2016

Abstract

Dyskeratosis congenita (DKC) is associated with impaired telomere maintenance and with clinical features of premature aging. In this study, we analysed global DNA methylation (DNAm) profiles of DKC patients. Age-associated DNAm changes were not generally accelerated in DKC, but there were significant differences to DNAm patterns of healthy controls, particularly in CpG sites related to an internal promoter region of PR domain containing 8 (PRDM8). Notably, the same genomic region was also hypermethylated in aplastic anemia (AA) – another bone marrow failure syndrome. Site-specific analysis of DNAm level in PRDM8 with pyrosequencing and MassARRAY validated aberrant hypermethylation in 11 DKC patients and 27 AA patients. Telomere length, measured by flow-FISH, did not directly correlate with DNAm in PRDM8. Therefore the two methods may be complementary to also identify patients with still normal telomere length. In conclusion, blood of DKC patients reveals aberrant DNAm patterns, albeit age-associated DNAm patterns are not generally accelerated. Aberrant hypermethylation is particularly observed in PRDM8 and this may support identification and classification of bone marrow failure syndromes.


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