EGAGenomicsMignon Lohhttps://ega-archive.org/dacs/EGAC00001000751EGAEGA DAC EGAC00001000751EGAmignon.loh@ucsf.eduJuvenile myelomonocytic leukemia (JMML) is a myeloproliferative disorder of childhood caused by mutations in the Ras pathway. Outcomes in JMML vary markedly from spontaneous resolution to rapid relapse after hematopoietic stem cell transplantation. Here, we hypothesized that DNA methylation patterns would help predict disease outcome and therefore performed genome-wide DNA methylation profiling in a cohort of 39 patients. Unsupervised hierarchical clustering identifies three clusters of patients. Importantly, these clusters differ significantly in terms of 4-year event-free survival, with the lowest methylation cluster having the highest rates of survival. These findings were validated in an independent cohort of 40 patients. Notably, all but one of 14 patients experiencing spontaneous resolution cluster together and closer to 22 healthy controls than to other JMML cases. Thus, we show that DNA methylation patterns in JMML are predictive of outcome and can identify the patients most likely to experience spontaneous resolution.Genome-wide DNA methylation is predictive of outcome in juvenile myelomonocytic leukemia.Stieglitz Elliot E, Mazor Tali T, Olshen Adam B AB, Geng Huimin H, Gelston Laura C LC, Akutagawa Jon J, Lipka Daniel B DB, Plass Christoph C, Flotho Christian C, Chehab Farid F FF, Braun Benjamin S BS, Costello Joseph F JF, Loh Mignon L MLJMML, leukemia, DNA, DNA methylation maintenance, DNA Methylations, DNA methylation, juvenile myelomonocytic, Methylations, Methylation, chronic myelomonocytic.Juvenile Myelomonocytic Leukemia, Juvenile, leukemia, Juvenile Myelomonocytic Leukemias, wide, Leukemia, DNA methylation maintenance, Myelomonocytic Leukemia, wide/broad, Genomes, juvenile myelomonocytic, Juvenile Myelomonocytic., DNA, Myelomonocytic Leukemias, whole genome, DNA Methylations, broad, DNA methylation, Methylations, Methylation, Juvenile Chronic Myelogenous Leukemia, chronic myelomonocyticJMML, Ras1/RAs85D, other disease, RAS, Ras, l(1)G0098, Disorders, RasV12, dRas, Kras2, Stem Cell Transplantation, CG1167, H-ras, c-rasHa, E(sev)3C, DRAS1, DRas2, DNA Methylations, DmelCG9375, IMPDH, broad, Ras-1, LD06825, CG11485, myeloproliferative neoplasms, Mutations, Dras2, Dras1, l(1)G0388, ras, relapse, c-ras2, Client., D-Ras, diseases, symptoms, Kras-2, disease or disorder, diseases and disorders, Relapses, IMPdH, Ha-ras, l(1)G0380, D-Ras1, Dras, p21B, ras 1, human disease, Leukemia, dras1, Dm-ras-64B, DNA methylation maintenance, RTK, juvenile myelomonocytic, Genomes, Recrudescences, raspberry/impd, l(1)G0436, Recurrences, U, ras85B, ras85D, DNA methylation, Ras[V12], l(1)G0391, EK3-4, free, Juvenile Myelomonocytic, DRas, non-neoplastic, DRas85D/Ras, Ras 85D, Dmras64B, D-ras-2, Myelomonocytic Leukemia, Myeloproliferative Disorder, chronic myeloproliferative disorders, time of survival, Clients, Disorder, disorder, Homo sapiens disease, ras-l, Methylations, CG1799, l(1)G0056, leukemia, Relapse, screening, l(3)s1747, findings, Ras2, RAS2, wide/broad, CG9375, Ras1, RAS1, Ki-ras, disorders, K-ras, Myelomonocytic Leukemias, medical condition, D-ras-1, Myeloproliferative, DNA methylation profiling, Client, Juvenile Myelomonocytic Leukemia, Juvenile, E(faf), DmelCG1167, fs(3)05703, survival, Recrudescence, EP(X)1093, dRas85D, Diseases, S35097, condition, p21[Ras1], dRas1, dRAS1, methylation, AI929937, ras1, Dras85D, ras2, ras-2, BcDNA:RE36103, CMPD, Juvenile Myelomonocytic Leukemias, RAS85D, Hematopoietic, l(1)G0351, Dmras85D, LD02673, death rate, l(1)9Eb, Transplantation, DmelCG1799, c-Ha-ras, D-ras1, l(1)G0238, D-ras2, Hras-1, C-ras1, signs, Dm Ras1, whole genome, Dras64B, Hematopoietic Stem Cell, Juvenile Chronic Myelogenous Leukemia, Su(tor)3-2, C-ras2, chronic myelomonocytic, l(3)06677, l(1)G0002, RasI, disease, l(1)G0482, wide, Patient, c-H-ras, l(1)G0127, DNA, Harvey-ras, Methylation, Hras1falseDNA Methylation in JMMLData Access Committee EGAC00001000751EGAC00001000751960629259179EGAS00001002700EGAD00010001449EGAD00010001450EGAD00001003794