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

Alexandra Søgaard Helbo; Marianne Bach Treppendahl; Derya Aslan; Konstantinos Dimopoulos; Cecilie Nandrup-Bus; Mette Skov Holm; Mette Klarskov Andersen; Gangning Liang; Lasse Sommer Kristensen; Kirsten Grønbæk

doi:10.3390/genes6040977

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

Alexandra Søgaard Helbo, Marianne Bach Treppendahl, Derya Aslan, Konstantinos Dimopoulos, Cecilie Nandrup-Bus, Mette Skov Holm, Mette Klarskov Andersen, Gangning Liang, Lasse Sommer Kristensen, Kirsten Grønbæk

10 Citations (Scopus)

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.

Original language	English
Journal	Genes
Volume	6
Issue number	4
Pages (from-to)	977-90
Number of pages	14
ISSN	2073-4425
DOIs	https://doi.org/10.3390/genes6040977
Publication status	Published - 14 Oct 2015

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@article{9854a2da98674142b55c6ee15632d0f5,

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

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.",

author = "Helbo, {Alexandra S{\o}gaard} and Treppendahl, {Marianne Bach} and Derya Aslan and Konstantinos Dimopoulos and Cecilie Nandrup-Bus and Holm, {Mette Skov} and Andersen, {Mette Klarskov} and Gangning Liang and {Sommer Kristensen}, Lasse and Kirsten Gr{\o}nb{\ae}k",

year = "2015",

month = oct,

day = "14",

doi = "10.3390/genes6040977",

language = "English",

volume = "6",

pages = "977--90",

journal = "Genes",

issn = "2073-4425",

publisher = "M D P I AG",

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TY - JOUR

T1 - Hypermethylation of the VTRNA1-3 Promoter is Associated with Poor Outcome in Lower Risk Myelodysplastic Syndrome Patients

AU - Helbo, Alexandra Søgaard

AU - Treppendahl, Marianne Bach

AU - Aslan, Derya

AU - Dimopoulos, Konstantinos

AU - Nandrup-Bus, Cecilie

AU - Holm, Mette Skov

AU - Andersen, Mette Klarskov

AU - Liang, Gangning

AU - Sommer Kristensen, Lasse

AU - Grønbæk, Kirsten

PY - 2015/10/14

Y1 - 2015/10/14

N2 - 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.

AB - 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.

U2 - 10.3390/genes6040977

DO - 10.3390/genes6040977

M3 - Journal article

C2 - 26473932

SN - 2073-4425

VL - 6

SP - 977

EP - 990

JO - Genes

JF - Genes

IS - 4

ER -

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

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