EGAGenomicsIllumina HiSeq 2000Otherhttps://ega-archive.org/studies/EGAS00001001264EGAEGA study EGAS00001001264CMML NGS data collection from Gustave RoussyEGArestrictedThe cytidine analogues azacytidine and 5-aza-2'-deoxycytidine (decitabine) are commonly used to treat myelodysplastic syndromes, with or without a myeloproliferative component. It remains unclear whether the response to these hypomethylating agents results from a cytotoxic or an epigenetic effect. In this study, we address this question in chronic myelomonocytic leukaemia. We describe a comprehensive analysis of the mutational landscape of these tumours, combining whole-exome and whole-genome sequencing. We identify an average of 14±5 somatic mutations in coding sequences of sorted monocyte DNA and the signatures of three mutational processes. Serial sequencing demonstrates that the response to hypomethylating agents is associated with changes in DNA methylation and gene expression, without any decrease in the mutation allele burden, nor prevention of new genetic alteration occurence. Our findings indicate that cytosine analogues restore a balanced haematopoiesis without decreasing the size of the mutated clone, arguing for a predominantly epigenetic effect.Mutation allele burden remains unchanged in chronic myelomonocytic leukaemia responding to hypomethylating agents.Merlevede Jane J, Droin Nathalie N, Qin Tingting T, Meldi Kristen K, Yoshida Kenichi K, Morabito Margot M, Chautard Emilie E, Auboeuf Didier D, Fenaux Pierre P, Braun Thorsten T, Itzykson Raphael R, de Botton Stéphane S, Quesnel Bruno B, Commes Thérèse T, Jourdan Eric E, Vainchenker William W, Bernard Olivier O, Pata-Merci Noemie N, Solier Stéphanie S, Gayevskiy Velimir V, Dinger Marcel E ME, Cowley Mark J MJ, Selimoglu-Buet Dorothée D, Meyer Vincent V, Artiguenave François F, Deleuze Jean-François JF, Preudhomme Claude C, Stratton Michael R MR, Alexandrov Ludmil B LB, Padron Eric E, Ogawa Seishi S, Koscielny Serge S, Figueroa Maria M, Solary Eric Echronic myelomonocytic leukemia (CMML), WGS, Whole Transcriptome Shotgun Sequencing, WES, CMML, RNA-seq., chronic myelomonocytic leukemia, chronic myelomonocytic leukaemia (CMML)leukemia, whole exome, Controlling, RNA, preventive therapy, DNS, RNA Sequence Determination, determination, (Deoxyribonucleotide)n, RNA Sequence Determinations, Sequence Determination, Chronic Myelomonocytic, DNAn+1, RNA Sequence, chronic myelomonocytic leukemia (CMML), CMML, Myelomonocytic Leukemias, DNA Methylations, Double-Stranded, Leukemias, prevention, Deoxyribonucleic acids, chronic myelomonocytic leukemia, Determinations, (Deoxyribonucleotide)n+m, Client., Deoxyribonucleic Acid, Chronic Myelomonocytic Leukemia, chemical analysis, sequence, Analysis, ds-DNA, desoxyribose nucleic acid, prevention and control, thymus nucleic acid, Leukemia, DNA methylation maintenance, reference sample, Genomes, juvenile myelomonocytic, Analyses, Determination, prophylaxis, Double Stranded, Deoxyribonucleic acid, whole genome, DNA methylation, Chronic Myelomonocytic Leukemias, Sequence Determinations, primary structure of sequence macromolecule, Sequencing, chronic myelomonocytic, preventive measures, Myelomonocytic Leukemia, RNA Sequence Analyses, Patient, control, Clients, RNA Sequence Analysis, ds DNA, chronic myelomonocytic leukaemia (CMML), Desoxyribonukleinsaeure, Chronic, RNA Sequencing, Double-Stranded DNA, assay, (Deoxyribonucleotide)m, DNA, deoxyribonucleic acids, DNAn, Methylations, Methylation, Controlled, Sequence AnalysesMutations, leukemia, Chronic, leukaemia.Vidaza, whole exome, 2'-Deoxy-5-azacytidine, mononuclear leukocyte, DNS, Zytidin, AzadC Compound, Myelodysplasia, determination, (Deoxyribonucleotide)n, neoplasia, Neoplasms, Addresses, Gene, Tumor, Medullary, Deoxyribonucleic acids, prevention, NEOPL, Riboside, protrusion, Medullary Hematopoiesis, Mutations, Deoxyribonucleic Acid, Epigenomic., symptoms, 1, Dysmyelopoietic Syndromes, 3, Decitabine Mesylate, 5-azadeoxycytidine, leukaemia, neoplasm, prevention and control, decitabine, average, study, C, thymus nucleic acid, NSC-102816, Hematopoetic Myelodysplasias, Gene Expressions, Dysmyelopoietic Syndrome, 5-Triazin-2(1H)-one, Genomes, AzadC, cell process disease, tumor disease, 5AzadC, neoplasm (disease), 5-Azadeoxycytidine, Cytidin, Double Stranded, 4-amino-2(1H)-pyrimidinone, 4-amino-1beta-D-ribofuranosyl-2(1H)-pyrimidinone, NSC 127716, tumour, Deoxyribonucleic acid, NSC-127716, 5 Deoxyazacytidine, Expressions, 4-amino-1-beta-D-ribofuranosyl-, NSC102816, Epigenomic, 5-Azacytidine, Myelodysplastic Syndromes, genetic, preventive measures, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS), Monocyte, 4-amino-1-beta-D-ribofuranosylpyrimidin-2(1H)-one, NSC 102816, Mesylate, Syndrome, Chronic, cytosine-1beta-D-Ribofuranoside, Double-Stranded DNA, (Deoxyribonucleotide)m, Expression, tumor, deoxyribonucleic acids, DNAn, monocyte, constitutitional genetic, myelodysplastic syndrome, Neoplastic Growth, nongranular leukocyte, Zytosin, 4-AMINO-1-BETA-D-RIBOFURANOSYL-2(1H)-PYRIMIDINONE, Tumors, leukemia, screening, Myelodysplastic Syndrome, 4-amino-, preventive therapy, 5 Azacytidine, anatomical protrusion, findings, DNAn+1, Cyd, 5 Aza 2' deoxycytidine, familial, 5-Aza-2'-deoxycytidine, changes in DNA methylation, Hematopoiesis, neoplastic disease, Double-Stranded, Cytosine, results, tumours, Cytosine riboside, Hematopoetic, Cyt, (Deoxyribonucleotide)n+m, Hematopoetic Myelodysplasia, neoplastic growth, 5-Deoxyazacytidine, 5-AzadC, chemical analysis, Dacogen, ds-DNA, desoxyribose nucleic acid, Cytosine Ribonucleoside, Azacytidine, 2(1H)-Pyrimidinone, Decitabine, 1beta-D-ribofuranosylcytosine, Epigenetic, 5 Azadeoxycytidine, prophylaxis, 2' Deoxy 5 azacytidine, susceptibility to, NSC127716, Exomes, signs, whole genome, Haematopoiesis, 4-amino-1-(2-deoxy-beta-D-erythro-pentofuranosyl)-s-triazin-2(1H)-one, disease of cellular proliferation, Myelodysplastic, 1-beta-D-Ribofuranosylcytosine, Cytosine Riboside, 4-amino-2-hydroxypyrimidine, Syndromes, Compound, Myelodysplasias, spine, control, ds DNA, Desoxyribonukleinsaeure, inherited genetic, assay, Cytosin, DNA, Epigenetics, other neoplasm, hereditary, Ribonucleoside, NEOPLASMS BENIGN, Neoplasia, DysmyelopoieticfalseCMML Collection of WES, WGS, RNA-Seq and ERRBS dataWe first performed a comprehensive analysis of the genome of 66 chronic myelomonocytic leukemia cases using whole exome (N=49) or whole genome (N=17) sequencing for paired leukemic-control DNA. Then, we realized serial analysis of whole exome sequence in 17 cases, completed with serial RNA sequencing and DNA methylation analysis in 9 cases, including patients treated or not with hypomethylating agents.2017-07-26 15:39:26EGAS00001001264960626908133EGAD00001001853EGAC00001000342