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Genes 2015, 6(4), 977-990; doi:10.3390/genes6040977

Hypermethylation of the VTRNA1-3 Promoter is Associated with Poor Outcome in Lower Risk Myelodysplastic Syndrome Patients

1
Department of Hematology, Rigshospitalet, University Hospital Copenhagen, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark
2
Department of Hematology, Aarhus University Hospital, Tage Hansens Gade 2, 8000 Aarhus C, Denmark
3
Department of Clinical Genetics, Rigshospitalet, University Hospital Copenhagen, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark
4
Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90089, USA
5
Danstem, University of Copenhagen, Blegdamsvej, 2200 Copenhagen N, Denmark
*
Author to whom correspondence should be addressed.
Academic Editors: Jeffrey Craig and Thomas Mikeska
Received: 8 July 2015 / Revised: 9 September 2015 / Accepted: 22 September 2015 / Published: 14 October 2015
(This article belongs to the Special Issue Epigenetic Biomarkers)
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Abstract

Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic disorders. MDS is frequently associated with deletions on chromosome 5q as well as aberrant DNA methylation patterns including hypermethylation of key tumor suppressors. We have previously shown that hypermethylation and silencing of the non-coding RNA VTRNA2-1 are correlated with poor outcomes in acute myeloid leukemia patients. In this study, we find that VTRNA1-2 and VTRNA1-3, both located on chromosome 5q, can be regulated and silenced by promoter DNA methylation, and that the hypomethylating agent 5-aza-2-deoxycytidine causes reactivation these genes. In normal hematopoiesis, we find that vault RNAs (vtRNAs) show differential methylation between various hematopoietic cell populations, indicating that allele-specific methylation events may occur during hematopoiesis. In addition, we show that VTRNA1-3 promoter hypermethylation is frequent in lower risk MDS patients and is associated with a decreased overall survival. View Full-Text
Keywords: DNA methylation; non-coding RNA; Myelodysplastic syndrome; Azanucleosides; vault RNA DNA methylation; non-coding RNA; Myelodysplastic syndrome; Azanucleosides; vault RNA
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Helbo, A.S.; Treppendahl, M.; Aslan, D.; Dimopoulos, K.; Nandrup-Bus, C.; Holm, M.S.; Andersen, M.K.; Liang, G.; Kristensen, L.S.; Grønbæk, K. Hypermethylation of the VTRNA1-3 Promoter is Associated with Poor Outcome in Lower Risk Myelodysplastic Syndrome Patients. Genes 2015, 6, 977-990.

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