Advanced search
1 file | 2.99 MB

RASA4 undergoes DNA hypermethylation in resistant juvenile myelomonocytic leukemia

(2014) EPIGENETICS. 9(9). p.1252-1260
Author
Organization
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.
Keywords
juvenile myelomonocytic leukemia, epigenetics, RASA4, JMML, DNA methylation, GAP1 FAMILY, GTPASE-ACTIVATING PROTEINS, PTPN11, MUTATIONS, CHILDHOOD, GENES, CHILDREN, PATHWAY, JMML

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 2.99 MB

Citation

Please use this url to cite or link to this publication:

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.
@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},
}

Altmetric
View in Altmetric
Web of Science
Times cited: