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000131643 1001_ $$00000-0001-5081-7869$$aLipka, Daniel B$$b0$$eFirst author
000131643 245__ $$aRAS-pathway mutation patterns define epigenetic subclasses in juvenile myelomonocytic leukemia.
000131643 260__ $$aLondon$$bNature Publishing Group$$c2017
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000131643 520__ $$aJuvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative disorder of early childhood characterized by mutations activating RAS signaling. Established clinical and genetic markers fail to fully recapitulate the clinical and biological heterogeneity of this disease. Here we report DNA methylome analysis and mutation profiling of 167 JMML samples. We identify three JMML subgroups with unique molecular and clinical characteristics. The high methylation group (HM) is characterized by somatic PTPN11 mutations and poor clinical outcome. The low methylation group is enriched for somatic NRAS and CBL mutations, as well as for Noonan patients, and has a good prognosis. The intermediate methylation group (IM) shows enrichment for monosomy 7 and somatic KRAS mutations. Hypermethylation is associated with repressed chromatin, genes regulated by RAS signaling, frequent co-occurrence of RAS pathway mutations and upregulation of DNMT1 and DNMT3B, suggesting a link between activation of the DNA methylation machinery and mutational patterns in JMML.
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000131643 7001_ $$00000-0003-4287-1608$$aWitte, Tania$$b1$$eFirst author
000131643 7001_ $$0P:(DE-He78)cd2ec3f2ae9b2178f113e0f2ed15fc48$$aToth, Reka$$b2$$udkfz
000131643 7001_ $$0P:(DE-He78)f408e260b87a089b925516846cebe59c$$aYang, Jing$$b3$$udkfz
000131643 7001_ $$0P:(DE-He78)1042737c83ba70ec508bdd99f0096864$$aWiesenfarth, Manuel$$b4$$udkfz
000131643 7001_ $$00000-0002-0281-4732$$aNöllke, Peter$$b5
000131643 7001_ $$aFischer, Alexandra$$b6
000131643 7001_ $$0P:(DE-He78)3860e24c3868c15255c3383a58e8d5b8$$aBrocks, David$$b7$$udkfz
000131643 7001_ $$0P:(DE-He78)73316f3cd41c27508dbb6f4c5e7e7a8a$$aGu, Zuguang$$b8$$udkfz
000131643 7001_ $$0P:(DE-He78)92e094eac4fff11dc500bf29667bbc8e$$aPark, Jeongbin$$b9$$udkfz
000131643 7001_ $$aStrahm, Brigitte$$b10
000131643 7001_ $$00000-0001-6638-9643$$aWlodarski, Marcin$$b11
000131643 7001_ $$aYoshimi, Ayami$$b12
000131643 7001_ $$aClaus, Rainer$$b13
000131643 7001_ $$aLübbert, Michael$$b14
000131643 7001_ $$aBusch, Hauke$$b15
000131643 7001_ $$aBoerries, Melanie$$b16
000131643 7001_ $$00000-0002-4072-4658$$aHartmann, Mark$$b17
000131643 7001_ $$00000-0002-9778-9698$$aSchönung, Maximilian$$b18
000131643 7001_ $$0P:(DE-He78)076ea1a7c623ab7e1b9a1c7824a12963$$aKilik, Umut$$b19$$udkfz
000131643 7001_ $$0P:(DE-He78)6c69bbe6493efcf728dd48d0257f4eda$$aLangstein, Jens$$b20$$udkfz
000131643 7001_ $$00000-0001-5536-3501$$aWierzbinska, Justyna A$$b21
000131643 7001_ $$aPabst, Caroline$$b22
000131643 7001_ $$aGarg, Swati$$b23
000131643 7001_ $$00000-0003-0133-1752$$aCatalá, Albert$$b24
000131643 7001_ $$aDe Moerloose, Barbara$$b25
000131643 7001_ $$aDworzak, Michael$$b26
000131643 7001_ $$00000-0003-3976-9231$$aHasle, Henrik$$b27
000131643 7001_ $$aLocatelli, Franco$$b28
000131643 7001_ $$00000-0002-1264-057X$$aMasetti, Riccardo$$b29
000131643 7001_ $$aSchmugge, Markus$$b30
000131643 7001_ $$aSmith, Owen$$b31
000131643 7001_ $$aStary, Jan$$b32
000131643 7001_ $$aUssowicz, Marek$$b33
000131643 7001_ $$avan den Heuvel-Eibrink, Marry M$$b34
000131643 7001_ $$0P:(DE-He78)45a6854ecf41ba2e65ca3ba0d560f14c$$aAssenov, Yassen$$b35$$udkfz
000131643 7001_ $$00000-0002-5896-4086$$aSchlesner, Matthias$$b36
000131643 7001_ $$aNiemeyer, Charlotte$$b37
000131643 7001_ $$aFlotho, Christian$$b38
000131643 7001_ $$00000-0003-2554-3952$$aPlass, Christoph$$b39
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