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@ARTICLE{Poetsch:120146,
author = {A. R. Poetsch$^*$ and D. Lipka$^*$ and T. Witte$^*$ and R.
Claus$^*$ and P. Nöllke and M. Zucknick$^*$ and C. Olk-Batz
and S. Fluhr and M. Dworzak and B. De Moerloose and J.
Starý and M. Zecca and H. Hasle and M. Schmugge and M. M.
van den Heuvel-Eibrink and F. Locatelli and C. M.
Niemeyer$^*$ and C. Flotho$^*$ and C. Plass$^*$},
title = {{RASA}4 undergoes {DNA} hypermethylation in resistant
juvenile myelomonocytic leukemia.},
journal = {Epigenetics},
volume = {9},
number = {9},
issn = {1559-2308},
address = {Austin, Tex.},
publisher = {Landes Bioscience},
reportid = {DKFZ-2017-00729},
pages = {1252 - 1260},
year = {2014},
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 = {Protein Isoforms (NLM Chemicals) / RASA4 protein, human
(NLM Chemicals) / ras GTPase-Activating Proteins (NLM
Chemicals) / PTPN11 protein, human (NLM Chemicals) / Protein
Tyrosine Phosphatase, Non-Receptor Type 11 (NLM Chemicals)},
cin = {C010 / C060 / L101 / L601},
ddc = {610},
cid = {I:(DE-He78)C010-20160331 / I:(DE-He78)C060-20160331 /
I:(DE-He78)L101-20160331 / I:(DE-He78)L601-20160331},
pnm = {313 - Cancer risk factors and prevention (POF3-313)},
pid = {G:(DE-HGF)POF3-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:25147919},
pmc = {pmc:PMC4169017},
doi = {10.4161/epi.29941},
url = {https://inrepo02.dkfz.de/record/120146},
}