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RASA4 undergoes DNA hypermethylation in resistant juvenile myelomonocytic leukemia

Anna R Poetsch, Daniel B Lipka, Tania Witte, Rainer Claus, Peter Nöllke, Manuela Zucknick, Christiane Olk-Batz, Silvia Fluhr, Michael Dworzak, Barbara De Moerloose UGent, et al. (2014) EPIGENETICS. 9(9). p.1252-1260
abstract
Aberrant DNA methylation at specific genetic loci is a key molecular feature of juvenile myelomonocytic leukemia (JMML) with poor prognosis. Using quantitative high-resolution mass spectrometry, we identified RASA4 isoform 2, which maps to chromosome 7 and encodes a member of the GAP1 family of GTPase-activating proteins for small G proteins, as a recurrent target of isoform-specific DNA hypermethylation in JMML (51% of 125 patients analyzed). RASA4 isoform 2 promoter methylation correlated with clinical parameters predicting poor prognosis (older age, elevated fetal hemoglobin), with higher risk of relapse after hematopoietic stem cell transplantation, and with PTPN11 mutation. The level of isoform 2 methylation increased in relapsed cases after transplantation. Interestingly, most JMML cases with monosomy 7 exhibited hypermethylation on the remaining RASA4 allele. The results corroborate the significance of epigenetic modifications in the phenotype of aggressive JMML.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
juvenile myelomonocytic leukemia, epigenetics, RASA4, JMML, DNA methylation, GAP1 FAMILY, GTPASE-ACTIVATING PROTEINS, PTPN11, MUTATIONS, CHILDHOOD, GENES, CHILDREN, PATHWAY, JMML
journal title
EPIGENETICS
Epigenetics
volume
9
issue
9
pages
1252 - 1260
Web of Science type
Article
Web of Science id
000342564500007
JCR category
GENETICS & HEREDITY
JCR impact factor
4.78 (2014)
JCR rank
30/167 (2014)
JCR quartile
1 (2014)
ISSN
1559-2294
DOI
10.4161/epi.29941
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
5867061
handle
http://hdl.handle.net/1854/LU-5867061
date created
2015-02-26 13:29:21
date last changed
2017-02-22 14:39:31
@article{5867061,
  abstract     = {Aberrant DNA methylation at specific genetic loci is a key molecular feature of juvenile myelomonocytic leukemia (JMML) with poor prognosis. Using quantitative high-resolution mass spectrometry, we identified RASA4 isoform 2, which maps to chromosome 7 and encodes a member of the GAP1 family of GTPase-activating proteins for small G proteins, as a recurrent target of isoform-specific DNA hypermethylation in JMML (51\% of 125 patients analyzed). RASA4 isoform 2 promoter methylation correlated with clinical parameters predicting poor prognosis (older age, elevated fetal hemoglobin), with higher risk of relapse after hematopoietic stem cell transplantation, and with PTPN11 mutation. The level of isoform 2 methylation increased in relapsed cases after transplantation. Interestingly, most JMML cases with monosomy 7 exhibited hypermethylation on the remaining RASA4 allele. The results corroborate the significance of epigenetic modifications in the phenotype of aggressive JMML.},
  author       = {Poetsch, Anna R and Lipka, Daniel B and Witte, Tania and Claus, Rainer and N{\"o}llke, Peter and Zucknick, Manuela and Olk-Batz, Christiane and Fluhr, Silvia and Dworzak, Michael and De Moerloose, Barbara and Star{\'y}, Jan and Zecca, Marco and Hasle, Henrik and Schmugge, Markus and van den Heuvel-Eibrink, Marry M and Locatelli, Franco and Niemeyer, Charlotte M and Flotho, Christian and Plass, Christoph},
  issn         = {1559-2294},
  journal      = {EPIGENETICS},
  keyword      = {juvenile myelomonocytic leukemia,epigenetics,RASA4,JMML,DNA methylation,GAP1 FAMILY,GTPASE-ACTIVATING PROTEINS,PTPN11,MUTATIONS,CHILDHOOD,GENES,CHILDREN,PATHWAY,JMML},
  language     = {eng},
  number       = {9},
  pages        = {1252--1260},
  title        = {RASA4 undergoes DNA hypermethylation in resistant juvenile myelomonocytic leukemia},
  url          = {http://dx.doi.org/10.4161/epi.29941},
  volume       = {9},
  year         = {2014},
}

Chicago
Poetsch, Anna R, Daniel B Lipka, Tania Witte, Rainer Claus, Peter Nöllke, Manuela Zucknick, Christiane Olk-Batz, et al. 2014. “RASA4 Undergoes DNA Hypermethylation in Resistant Juvenile Myelomonocytic Leukemia.” Epigenetics 9 (9): 1252–1260.
APA
Poetsch, A. R., Lipka, D. B., Witte, T., Claus, R., Nöllke, P., Zucknick, M., Olk-Batz, C., et al. (2014). RASA4 undergoes DNA hypermethylation in resistant juvenile myelomonocytic leukemia. EPIGENETICS, 9(9), 1252–1260.
Vancouver
1.
Poetsch AR, Lipka DB, Witte T, Claus R, Nöllke P, Zucknick M, et al. RASA4 undergoes DNA hypermethylation in resistant juvenile myelomonocytic leukemia. EPIGENETICS. 2014;9(9):1252–60.
MLA
Poetsch, Anna R, Daniel B Lipka, Tania Witte, et al. “RASA4 Undergoes DNA Hypermethylation in Resistant Juvenile Myelomonocytic Leukemia.” EPIGENETICS 9.9 (2014): 1252–1260. Print.