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000120146 1001_ $$0P:(DE-HGF)0$$aPoetsch, Anna R$$b0$$eFirst author
000120146 245__ $$aRASA4 undergoes DNA hypermethylation in resistant juvenile myelomonocytic leukemia.
000120146 260__ $$aAustin, Tex.$$bLandes Bioscience$$c2014
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000120146 520__ $$aAberrant DNA methylation at specific genetic loci is a key molecular feature of juvenile myelomonocytic leukemia (JMML) with poor prognosis. Using quantitative high-resolution mass spectrometry, we identified RASA4 isoform 2, which maps to chromosome 7 and encodes a member of the GAP1 family of GTPase-activating proteins for small G proteins, as a recurrent target of isoform-specific DNA hypermethylation in JMML (51% of 125 patients analyzed). RASA4 isoform 2 promoter methylation correlated with clinical parameters predicting poor prognosis (older age, elevated fetal hemoglobin), with higher risk of relapse after hematopoietic stem cell transplantation, and with PTPN11 mutation. The level of isoform 2 methylation increased in relapsed cases after transplantation. Interestingly, most JMML cases with monosomy 7 exhibited hypermethylation on the remaining RASA4 allele. The results corroborate the significance of epigenetic modifications in the phenotype of aggressive JMML.
000120146 536__ $$0G:(DE-HGF)POF3-313$$a313 - Cancer risk factors and prevention (POF3-313)$$cPOF3-313$$fPOF III$$x0
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000120146 650_7 $$2NLM Chemicals$$aProtein Isoforms
000120146 650_7 $$2NLM Chemicals$$aRASA4 protein, human
000120146 650_7 $$2NLM Chemicals$$aras GTPase-Activating Proteins
000120146 650_7 $$0EC 3.1.3.48$$2NLM Chemicals$$aPTPN11 protein, human
000120146 650_7 $$0EC 3.1.3.48$$2NLM Chemicals$$aProtein Tyrosine Phosphatase, Non-Receptor Type 11
000120146 7001_ $$0P:(DE-He78)c403a040c97f91902a7d31b93859f9fc$$aLipka, Daniel$$b1$$udkfz
000120146 7001_ $$0P:(DE-HGF)0$$aWitte, Tania$$b2
000120146 7001_ $$0P:(DE-HGF)0$$aClaus, Rainer$$b3
000120146 7001_ $$aNöllke, Peter$$b4
000120146 7001_ $$0P:(DE-HGF)0$$aZucknick, Manuela$$b5
000120146 7001_ $$aOlk-Batz, Christiane$$b6
000120146 7001_ $$aFluhr, Silvia$$b7
000120146 7001_ $$aDworzak, Michael$$b8
000120146 7001_ $$aDe Moerloose, Barbara$$b9
000120146 7001_ $$aStarý, Jan$$b10
000120146 7001_ $$aZecca, Marco$$b11
000120146 7001_ $$aHasle, Henrik$$b12
000120146 7001_ $$aSchmugge, Markus$$b13
000120146 7001_ $$avan den Heuvel-Eibrink, Marry M$$b14
000120146 7001_ $$aLocatelli, Franco$$b15
000120146 7001_ $$0P:(DE-HGF)0$$aNiemeyer, Charlotte M$$b16
000120146 7001_ $$0P:(DE-HGF)0$$aFlotho, Christian$$b17
000120146 7001_ $$0P:(DE-He78)4301875630bc997edf491c694ae1f8a9$$aPlass, Christoph$$b18$$eLast author$$udkfz
000120146 773__ $$0PERI:(DE-600)2248598-3$$a10.4161/epi.29941$$gVol. 9, no. 9, p. 1252 - 1260$$n9$$p1252 - 1260$$tEpigenetics$$v9$$x1559-2308$$y2014
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