Mutation allele burden remains unchanged in chronic myelomonocytic leukaemia responding to hypomethylating agents
Identifieur interne : 001A78 ( Main/Exploration ); précédent : 001A77; suivant : 001A79Mutation allele burden remains unchanged in chronic myelomonocytic leukaemia responding to hypomethylating agents
Auteurs : Jane Merlevede [France] ; Nathalie Droin [France] ; Tingting Qin [États-Unis] ; Kristen Meldi [États-Unis] ; Kenichi Yoshida [Japon] ; Margot Morabito [France] ; Emilie Chautard [France] ; Didier Auboeuf [France] ; Pierre Fenaux [France] ; Thorsten Braun [France] ; Raphael Itzykson [France] ; Stéphane De Botton [France] ; Bruno Quesnel [France] ; Thérèse Commes [France] ; Eric Jourdan [France] ; William Vainchenker [France] ; Olivier Bernard [France] ; Noemie Pata-Merci [France] ; Stéphanie Solier [France] ; Velimir Gayevskiy [Australie] ; Marcel E. Dinger [Australie] ; Mark J. Cowley [Australie] ; Dorothée Selimoglu-Buet [France] ; Vincent Meyer [France] ; François Artiguenave [France] ; Jean-François Deleuze [France] ; Claude Preudhomme [France] ; Michael R. Stratton [Royaume-Uni] ; Ludmil B. Alexandrov [Royaume-Uni, États-Unis] ; Eric Padron [États-Unis] ; Seishi Ogawa [Japon] ; Serge Koscielny [France] ; Maria Figueroa [États-Unis] ; Eric Solary [France]Source :
- Nature Communications [ 2041-1723 ] ; 2016.
Descripteurs français
- KwdFr :
- Adulte d'âge moyen, Allèles, Analyse de séquence d'ADN, Analyse de séquence d'ARN, Antinéoplasiques antimétabolites (pharmacologie), Antinéoplasiques antimétabolites (usage thérapeutique), Azacitidine (analogues et dérivés), Azacitidine (pharmacologie), Azacitidine (usage thérapeutique), Cellules HEK293, Femelle, Humains, Leucémie myélomonocytaire chronique (génétique), Leucémie myélomonocytaire chronique (traitement médicamenteux), Mutation, Mâle, Méthylation de l'ADN (), Régulation de l'expression des gènes tumoraux (), Sujet âgé, Sujet âgé de 80 ans ou plus, Survie cellulaire (), Séquençage nucléotidique à haut débit, Épigenèse génétique ().
- MESH :
- analogues et dérivés : Azacitidine.
- génétique : Leucémie myélomonocytaire chronique.
- pharmacologie : Antinéoplasiques antimétabolites, Azacitidine.
- traitement médicamenteux : Leucémie myélomonocytaire chronique.
- usage thérapeutique : Antinéoplasiques antimétabolites, Azacitidine.
- Adulte d'âge moyen, Allèles, Analyse de séquence d'ADN, Analyse de séquence d'ARN, Cellules HEK293, Femelle, Humains, Mutation, Mâle, Méthylation de l'ADN, Régulation de l'expression des gènes tumoraux, Sujet âgé, Sujet âgé de 80 ans ou plus, Survie cellulaire, Séquençage nucléotidique à haut débit, Épigenèse génétique.
English descriptors
- KwdEn :
- Aged, Aged, 80 and over, Alleles, Antimetabolites, Antineoplastic (pharmacology), Antimetabolites, Antineoplastic (therapeutic use), Azacitidine (analogs & derivatives), Azacitidine (pharmacology), Azacitidine (therapeutic use), Cell Survival (drug effects), DNA Methylation (drug effects), Epigenesis, Genetic (drug effects), Female, Gene Expression Regulation, Neoplastic (drug effects), HEK293 Cells, High-Throughput Nucleotide Sequencing, Humans, Leukemia, Myelomonocytic, Chronic (drug therapy), Leukemia, Myelomonocytic, Chronic (genetics), Male, Middle Aged, Mutation, Sequence Analysis, DNA, Sequence Analysis, RNA.
- MESH :
- chemical , analogs & derivatives : Azacitidine.
- chemical , pharmacology : Antimetabolites, Antineoplastic, Azacitidine.
- chemical , therapeutic use : Antimetabolites, Antineoplastic, Azacitidine.
- drug effects : Cell Survival, DNA Methylation, Epigenesis, Genetic, Gene Expression Regulation, Neoplastic.
- drug therapy : Leukemia, Myelomonocytic, Chronic.
- genetics : Leukemia, Myelomonocytic, Chronic.
- Aged, Aged, 80 and over, Alleles, Female, HEK293 Cells, High-Throughput Nucleotide Sequencing, Humans, Male, Middle Aged, Mutation, Sequence Analysis, DNA, Sequence Analysis, RNA.
Abstract
The 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.
Url:
DOI: 10.1038/ncomms10767
PubMed: 26908133
PubMed Central: 4770084
Affiliations:
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Le document en format XML
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93000 Bobigny,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Itzykson, Raphael" sort="Itzykson, Raphael" uniqKey="Itzykson R" first="Raphael" last="Itzykson">Raphael Itzykson</name><affiliation wicri:level="1"><nlm:aff id="a8"><institution>Department of Hematology, Assistance Publique–Hôpitaux de Paris, Hôpital Saint-Louis</institution>, 1 Avenue Claude Vellefaux, 75010 Paris,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="De Botton, Stephane" sort="De Botton, Stephane" uniqKey="De Botton S" first="Stéphane" last="De Botton">Stéphane De Botton</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>INSERM U1170, Gustave Roussy</institution>, 114, rue Edouard Vaillant, 94805 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strict</wicri:regionArea></affiliation></author><author><name sortKey="Vainchenker, William" sort="Vainchenker, William" uniqKey="Vainchenker W" first="William" last="Vainchenker">William Vainchenker</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>INSERM U1170, Gustave Roussy</institution>, 114, rue Edouard Vaillant, 94805 Villejuif,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Hematology, Gustave Roussy Cancer Center</institution>, 114, rue Edouard Vaillant, 94805 Villejuif,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bernard, Olivier" sort="Bernard, Olivier" uniqKey="Bernard O" first="Olivier" last="Bernard">Olivier Bernard</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>INSERM U1170, Gustave Roussy</institution>, 114, rue Edouard Vaillant, 94805 Villejuif,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Hematology, Gustave Roussy Cancer Center</institution>, 114, rue Edouard Vaillant, 94805 Villejuif,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Pata Merci, Noemie" sort="Pata Merci, Noemie" uniqKey="Pata Merci N" first="Noemie" last="Pata-Merci">Noemie Pata-Merci</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>INSERM US23, CNRS UMS3655, Gustave Roussy</institution>, 114, rue Edouard Vaillant, 94805 Villejuif,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Solier, Stephanie" sort="Solier, Stephanie" uniqKey="Solier S" first="Stéphanie" last="Solier">Stéphanie Solier</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>INSERM U1170, Gustave Roussy</institution>, 114, rue Edouard Vaillant, 94805 Villejuif,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Hematology, Gustave Roussy Cancer Center</institution>, 114, rue Edouard Vaillant, 94805 Villejuif,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Gayevskiy, Velimir" sort="Gayevskiy, Velimir" uniqKey="Gayevskiy V" first="Velimir" last="Gayevskiy">Velimir Gayevskiy</name><affiliation wicri:level="1"><nlm:aff id="a13"><institution>Laboratory of Genome Informatics, Kinghor Center for Clinical Genomics, Garvan Institute of Medical Research</institution>, 384 Victoria Street, Darlinghurst New South Wales 2010,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Dinger, Marcel E" sort="Dinger, Marcel E" uniqKey="Dinger M" first="Marcel E." last="Dinger">Marcel E. Dinger</name><affiliation wicri:level="1"><nlm:aff id="a13"><institution>Laboratory of Genome Informatics, Kinghor Center for Clinical Genomics, Garvan Institute of Medical Research</institution>, 384 Victoria Street, Darlinghurst New South Wales 2010,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Cowley, Mark J" sort="Cowley, Mark J" uniqKey="Cowley M" first="Mark J." last="Cowley">Mark J. Cowley</name><affiliation wicri:level="1"><nlm:aff id="a13"><institution>Laboratory of Genome Informatics, Kinghor Center for Clinical Genomics, Garvan Institute of Medical Research</institution>, 384 Victoria Street, Darlinghurst New South Wales 2010,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Selimoglu Buet, Dorothee" sort="Selimoglu Buet, Dorothee" uniqKey="Selimoglu Buet D" first="Dorothée" last="Selimoglu-Buet">Dorothée Selimoglu-Buet</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>INSERM U1170, Gustave Roussy</institution>, 114, rue Edouard Vaillant, 94805 Villejuif,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Hematology, Gustave Roussy Cancer Center</institution>, 114, rue Edouard Vaillant, 94805 Villejuif,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Meyer, Vincent" sort="Meyer, Vincent" uniqKey="Meyer V" first="Vincent" last="Meyer">Vincent Meyer</name><affiliation wicri:level="1"><nlm:aff id="a14"><institution>Centre National de Génotypage</institution>, 2 rue Gaston Crémieux CP 5721, 91 057 Evry,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Artiguenave, Francois" sort="Artiguenave, Francois" uniqKey="Artiguenave F" first="François" last="Artiguenave">François Artiguenave</name><affiliation wicri:level="1"><nlm:aff id="a14"><institution>Centre National de Génotypage</institution>, 2 rue Gaston Crémieux CP 5721, 91 057 Evry,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Deleuze, Jean Francois" sort="Deleuze, Jean Francois" uniqKey="Deleuze J" first="Jean-François" last="Deleuze">Jean-François Deleuze</name><affiliation wicri:level="1"><nlm:aff id="a14"><institution>Centre National de Génotypage</institution>, 2 rue Gaston Crémieux CP 5721, 91 057 Evry,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Preudhomme, Claude" sort="Preudhomme, Claude" uniqKey="Preudhomme C" first="Claude" last="Preudhomme">Claude Preudhomme</name><affiliation wicri:level="1"><nlm:aff id="a10"><institution>Cancer Research Institute de Lille, INSERM U837</institution>, 1 Place de Verdun, 59000 Lille,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Stratton, Michael R" sort="Stratton, Michael R" uniqKey="Stratton M" first="Michael R." last="Stratton">Michael R. Stratton</name><affiliation wicri:level="1"><nlm:aff id="a15"><institution>Cancer Genome Project, Wellcome Trust Sanger Institute</institution>, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Alexandrov, Ludmil B" sort="Alexandrov, Ludmil B" uniqKey="Alexandrov L" first="Ludmil B." last="Alexandrov">Ludmil B. Alexandrov</name><affiliation wicri:level="1"><nlm:aff id="a15"><institution>Cancer Genome Project, Wellcome Trust Sanger Institute</institution>, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a16"><institution>Theoretical Biology and Biophysics, Los Alamos National Laboratory</institution>, P.O. Box 1663, Los Alamos, New Mexico 87545,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a17"><institution>Center for Nonlinear Studies, Los Alamos National Laboratory</institution>, P.O. Box 1663, Los Alamos, New Mexico 87545,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Padron, Eric" sort="Padron, Eric" uniqKey="Padron E" first="Eric" last="Padron">Eric Padron</name><affiliation wicri:level="1"><nlm:aff id="a18"><institution>Department of Hematology, Malignant hematology, H. Lee Moffitt Cancer Center</institution>, 12902 USF Magnolia Drive, Tampa, Florida 33612,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ogawa, Seishi" sort="Ogawa, Seishi" uniqKey="Ogawa S" first="Seishi" last="Ogawa">Seishi Ogawa</name><affiliation wicri:level="1"><nlm:aff id="a5"><institution>Department of Pathology and Tumour Biology, Kyoto University</institution>, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Koscielny, Serge" sort="Koscielny, Serge" uniqKey="Koscielny S" first="Serge" last="Koscielny">Serge Koscielny</name><affiliation wicri:level="1"><nlm:aff id="a19"><institution>Department of Biostatistics, Gustave Roussy Cancer Center</institution>, 114 rue Edouard Vaillant, 94805 Villejuif,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Figueroa, Maria" sort="Figueroa, Maria" uniqKey="Figueroa M" first="Maria" last="Figueroa">Maria Figueroa</name><affiliation wicri:level="1"><nlm:aff id="a4"><institution>Department of Pathology, University of Michigan Medical School</institution>, 1500 E Medical Center Dr, Ann Arbor, Michigan 48109,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Solary, Eric" sort="Solary, Eric" uniqKey="Solary E" first="Eric" last="Solary">Eric Solary</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>INSERM U1170, Gustave Roussy</institution>, 114, rue Edouard Vaillant, 94805 Villejuif,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Hematology, Gustave Roussy Cancer Center</institution>, 114, rue Edouard Vaillant, 94805 Villejuif,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a20"><institution>Department of Hematology, Faculty of Medicine, University Paris-Sud</institution>, 63 Rue Gabriel Péri, 94270 Le Kremlin-Bicêtre,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26908133</idno><idno type="pmc">4770084</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4770084</idno><idno type="RBID">PMC:4770084</idno><idno type="doi">10.1038/ncomms10767</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">000759</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000759</idno><idno type="wicri:Area/Pmc/Curation">000758</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000758</idno><idno type="wicri:Area/Pmc/Checkpoint">000755</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000755</idno><idno type="wicri:source">PubMed</idno><idno type="wicri:Area/PubMed/Corpus">002227</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002227</idno><idno type="wicri:Area/PubMed/Curation">002201</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002201</idno><idno type="wicri:Area/PubMed/Checkpoint">002201</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">002201</idno><idno type="wicri:Area/Ncbi/Merge">003177</idno><idno type="wicri:Area/Ncbi/Curation">003177</idno><idno type="wicri:Area/Ncbi/Checkpoint">003177</idno><idno type="wicri:Area/Main/Merge">001A74</idno><idno type="wicri:Area/Main/Curation">001A78</idno><idno type="wicri:Area/Main/Exploration">001A78</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Mutation allele burden remains unchanged in chronic myelomonocytic leukaemia responding to hypomethylating agents</title><author><name sortKey="Merlevede, Jane" sort="Merlevede, Jane" uniqKey="Merlevede J" first="Jane" last="Merlevede">Jane Merlevede</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>INSERM U1170, Gustave Roussy</institution>, 114, rue Edouard Vaillant, 94805 Villejuif,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Hematology, Gustave Roussy Cancer Center</institution>, 114, rue Edouard Vaillant, 94805 Villejuif,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Droin, Nathalie" sort="Droin, Nathalie" uniqKey="Droin N" first="Nathalie" last="Droin">Nathalie Droin</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>INSERM U1170, Gustave Roussy</institution>, 114, rue Edouard Vaillant, 94805 Villejuif,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Hematology, Gustave Roussy Cancer Center</institution>, 114, rue Edouard Vaillant, 94805 Villejuif,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a3"><institution>INSERM US23, CNRS UMS3655, Gustave Roussy</institution>, 114, rue Edouard Vaillant, 94805 Villejuif,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Qin, Tingting" sort="Qin, Tingting" uniqKey="Qin T" first="Tingting" last="Qin">Tingting Qin</name><affiliation wicri:level="1"><nlm:aff id="a4"><institution>Department of Pathology, University of Michigan Medical School</institution>, 1500 E Medical Center Dr, Ann Arbor, Michigan 48109,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Meldi, Kristen" sort="Meldi, Kristen" uniqKey="Meldi K" first="Kristen" last="Meldi">Kristen Meldi</name><affiliation wicri:level="1"><nlm:aff id="a4"><institution>Department of Pathology, University of Michigan Medical School</institution>, 1500 E Medical Center Dr, Ann Arbor, Michigan 48109,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Yoshida, Kenichi" sort="Yoshida, Kenichi" uniqKey="Yoshida K" first="Kenichi" last="Yoshida">Kenichi Yoshida</name><affiliation wicri:level="1"><nlm:aff id="a5"><institution>Department of Pathology and Tumour Biology, Kyoto University</institution>, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Morabito, Margot" sort="Morabito, Margot" uniqKey="Morabito M" first="Margot" last="Morabito">Margot Morabito</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>INSERM U1170, Gustave Roussy</institution>, 114, rue Edouard Vaillant, 94805 Villejuif,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Hematology, Gustave Roussy Cancer Center</institution>, 114, rue Edouard Vaillant, 94805 Villejuif,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Chautard, Emilie" sort="Chautard, Emilie" uniqKey="Chautard E" first="Emilie" last="Chautard">Emilie Chautard</name><affiliation wicri:level="1"><nlm:aff id="a6"><institution>Université Lyon 1, UMR CNRS 5558, Université Claude Bernard</institution>, 16 rue Raphael Dubois, Lyon 69100,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Auboeuf, Didier" sort="Auboeuf, Didier" uniqKey="Auboeuf D" first="Didier" last="Auboeuf">Didier Auboeuf</name><affiliation wicri:level="1"><nlm:aff id="a7"><institution>Centre Léon Bérard, INSERM U1052, CNRS UMR5286</institution>, 8 Prom. Léa et Napoléon Bullukian, 69008 Lyon,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Fenaux, Pierre" sort="Fenaux, Pierre" uniqKey="Fenaux P" first="Pierre" last="Fenaux">Pierre Fenaux</name><affiliation wicri:level="1"><nlm:aff id="a8"><institution>Department of Hematology, Assistance Publique–Hôpitaux de Paris, Hôpital Saint-Louis</institution>, 1 Avenue Claude Vellefaux, 75010 Paris,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Braun, Thorsten" sort="Braun, Thorsten" uniqKey="Braun T" first="Thorsten" last="Braun">Thorsten Braun</name><affiliation wicri:level="1"><nlm:aff id="a9"><institution>Department of Hematology, Assistance Publique–Hôpitaux de Paris</institution>, Hôpital Avicenne, 125 Rue de Stalingrad, 93000 Bobigny,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Itzykson, Raphael" sort="Itzykson, Raphael" uniqKey="Itzykson R" first="Raphael" last="Itzykson">Raphael Itzykson</name><affiliation wicri:level="1"><nlm:aff id="a8"><institution>Department of Hematology, Assistance Publique–Hôpitaux de Paris, Hôpital Saint-Louis</institution>, 1 Avenue Claude Vellefaux, 75010 Paris,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="De Botton, Stephane" sort="De Botton, Stephane" uniqKey="De Botton S" first="Stéphane" last="De Botton">Stéphane De Botton</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>INSERM U1170, Gustave Roussy</institution>, 114, rue Edouard Vaillant, 94805 Villejuif,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Hematology, Gustave Roussy Cancer Center</institution>, 114, rue Edouard Vaillant, 94805 Villejuif,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Quesnel, Bruno" sort="Quesnel, Bruno" uniqKey="Quesnel B" first="Bruno" last="Quesnel">Bruno Quesnel</name><affiliation wicri:level="1"><nlm:aff id="a10"><institution>Cancer Research Institute de Lille, INSERM U837</institution>, 1 Place de Verdun, 59000 Lille,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Commes, Therese" sort="Commes, Therese" uniqKey="Commes T" first="Thérèse" last="Commes">Thérèse Commes</name><affiliation wicri:level="1"><nlm:aff id="a11"><institution>Institut de médecine régénératrice, Biothérapie et Institut de biologie computationnelle, INSERM U1040, Université de Montpellier</institution>, 80 avenue Augustin Fliche. 34295 Montpellier,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Jourdan, Eric" sort="Jourdan, Eric" uniqKey="Jourdan E" first="Eric" last="Jourdan">Eric Jourdan</name><affiliation wicri:level="1"><nlm:aff id="a12"><institution>Department of Hematology, Centre Hospitalier Universitaire de Nîmes, Université Montpellier-Nîmes</institution>, 4 Rue du Professeur Robert Debré, 30029 Nîmes,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Vainchenker, William" sort="Vainchenker, William" uniqKey="Vainchenker W" first="William" last="Vainchenker">William Vainchenker</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>INSERM U1170, Gustave Roussy</institution>, 114, rue Edouard Vaillant, 94805 Villejuif,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Hematology, Gustave Roussy Cancer Center</institution>, 114, rue Edouard Vaillant, 94805 Villejuif,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bernard, Olivier" sort="Bernard, Olivier" uniqKey="Bernard O" first="Olivier" last="Bernard">Olivier Bernard</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>INSERM U1170, Gustave Roussy</institution>, 114, rue Edouard Vaillant, 94805 Villejuif,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Hematology, Gustave Roussy Cancer Center</institution>, 114, rue Edouard Vaillant, 94805 Villejuif,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Pata Merci, Noemie" sort="Pata Merci, Noemie" uniqKey="Pata Merci N" first="Noemie" last="Pata-Merci">Noemie Pata-Merci</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>INSERM US23, CNRS UMS3655, Gustave Roussy</institution>, 114, rue Edouard Vaillant, 94805 Villejuif,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Solier, Stephanie" sort="Solier, Stephanie" uniqKey="Solier S" first="Stéphanie" last="Solier">Stéphanie Solier</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>INSERM U1170, Gustave Roussy</institution>, 114, rue Edouard Vaillant, 94805 Villejuif,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Hematology, Gustave Roussy Cancer Center</institution>, 114, rue Edouard Vaillant, 94805 Villejuif,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Gayevskiy, Velimir" sort="Gayevskiy, Velimir" uniqKey="Gayevskiy V" first="Velimir" last="Gayevskiy">Velimir Gayevskiy</name><affiliation wicri:level="1"><nlm:aff id="a13"><institution>Laboratory of Genome Informatics, Kinghor Center for Clinical Genomics, Garvan Institute of Medical Research</institution>, 384 Victoria Street, Darlinghurst New South Wales 2010,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Dinger, Marcel E" sort="Dinger, Marcel E" uniqKey="Dinger M" first="Marcel E." last="Dinger">Marcel E. Dinger</name><affiliation wicri:level="1"><nlm:aff id="a13"><institution>Laboratory of Genome Informatics, Kinghor Center for Clinical Genomics, Garvan Institute of Medical Research</institution>, 384 Victoria Street, Darlinghurst New South Wales 2010,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Cowley, Mark J" sort="Cowley, Mark J" uniqKey="Cowley M" first="Mark J." last="Cowley">Mark J. Cowley</name><affiliation wicri:level="1"><nlm:aff id="a13"><institution>Laboratory of Genome Informatics, Kinghor Center for Clinical Genomics, Garvan Institute of Medical Research</institution>, 384 Victoria Street, Darlinghurst New South Wales 2010,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Selimoglu Buet, Dorothee" sort="Selimoglu Buet, Dorothee" uniqKey="Selimoglu Buet D" first="Dorothée" last="Selimoglu-Buet">Dorothée Selimoglu-Buet</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>INSERM U1170, Gustave Roussy</institution>, 114, rue Edouard Vaillant, 94805 Villejuif,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Hematology, Gustave Roussy Cancer Center</institution>, 114, rue Edouard Vaillant, 94805 Villejuif,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Meyer, Vincent" sort="Meyer, Vincent" uniqKey="Meyer V" first="Vincent" last="Meyer">Vincent Meyer</name><affiliation wicri:level="1"><nlm:aff id="a14"><institution>Centre National de Génotypage</institution>, 2 rue Gaston Crémieux CP 5721, 91 057 Evry,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Artiguenave, Francois" sort="Artiguenave, Francois" uniqKey="Artiguenave F" first="François" last="Artiguenave">François Artiguenave</name><affiliation wicri:level="1"><nlm:aff id="a14"><institution>Centre National de Génotypage</institution>, 2 rue Gaston Crémieux CP 5721, 91 057 Evry,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Deleuze, Jean Francois" sort="Deleuze, Jean Francois" uniqKey="Deleuze J" first="Jean-François" last="Deleuze">Jean-François Deleuze</name><affiliation wicri:level="1"><nlm:aff id="a14"><institution>Centre National de Génotypage</institution>, 2 rue Gaston Crémieux CP 5721, 91 057 Evry,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Preudhomme, Claude" sort="Preudhomme, Claude" uniqKey="Preudhomme C" first="Claude" last="Preudhomme">Claude Preudhomme</name><affiliation wicri:level="1"><nlm:aff id="a10"><institution>Cancer Research Institute de Lille, INSERM U837</institution>, 1 Place de Verdun, 59000 Lille,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Stratton, Michael R" sort="Stratton, Michael R" uniqKey="Stratton M" first="Michael R." last="Stratton">Michael R. Stratton</name><affiliation wicri:level="1"><nlm:aff id="a15"><institution>Cancer Genome Project, Wellcome Trust Sanger Institute</institution>, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Alexandrov, Ludmil B" sort="Alexandrov, Ludmil B" uniqKey="Alexandrov L" first="Ludmil B." last="Alexandrov">Ludmil B. Alexandrov</name><affiliation wicri:level="1"><nlm:aff id="a15"><institution>Cancer Genome Project, Wellcome Trust Sanger Institute</institution>, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA,<country>UK</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a16"><institution>Theoretical Biology and Biophysics, Los Alamos National Laboratory</institution>, P.O. Box 1663, Los Alamos, New Mexico 87545,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a17"><institution>Center for Nonlinear Studies, Los Alamos National Laboratory</institution>, P.O. Box 1663, Los Alamos, New Mexico 87545,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Padron, Eric" sort="Padron, Eric" uniqKey="Padron E" first="Eric" last="Padron">Eric Padron</name><affiliation wicri:level="1"><nlm:aff id="a18"><institution>Department of Hematology, Malignant hematology, H. Lee Moffitt Cancer Center</institution>, 12902 USF Magnolia Drive, Tampa, Florida 33612,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ogawa, Seishi" sort="Ogawa, Seishi" uniqKey="Ogawa S" first="Seishi" last="Ogawa">Seishi Ogawa</name><affiliation wicri:level="1"><nlm:aff id="a5"><institution>Department of Pathology and Tumour Biology, Kyoto University</institution>, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501,<country>Japan</country></nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Koscielny, Serge" sort="Koscielny, Serge" uniqKey="Koscielny S" first="Serge" last="Koscielny">Serge Koscielny</name><affiliation wicri:level="1"><nlm:aff id="a19"><institution>Department of Biostatistics, Gustave Roussy Cancer Center</institution>, 114 rue Edouard Vaillant, 94805 Villejuif,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Figueroa, Maria" sort="Figueroa, Maria" uniqKey="Figueroa M" first="Maria" last="Figueroa">Maria Figueroa</name><affiliation wicri:level="1"><nlm:aff id="a4"><institution>Department of Pathology, University of Michigan Medical School</institution>, 1500 E Medical Center Dr, Ann Arbor, Michigan 48109,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Solary, Eric" sort="Solary, Eric" uniqKey="Solary E" first="Eric" last="Solary">Eric Solary</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>INSERM U1170, Gustave Roussy</institution>, 114, rue Edouard Vaillant, 94805 Villejuif,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Hematology, Gustave Roussy Cancer Center</institution>, 114, rue Edouard Vaillant, 94805 Villejuif,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a20"><institution>Department of Hematology, Faculty of Medicine, University Paris-Sud</institution>, 63 Rue Gabriel Péri, 94270 Le Kremlin-Bicêtre,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Nature Communications</title><idno type="eISSN">2041-1723</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term><term>Aged, 80 and over</term><term>Alleles</term><term>Antimetabolites, Antineoplastic (pharmacology)</term><term>Antimetabolites, Antineoplastic (therapeutic use)</term><term>Azacitidine (analogs & derivatives)</term><term>Azacitidine (pharmacology)</term><term>Azacitidine (therapeutic use)</term><term>Cell Survival (drug effects)</term><term>DNA Methylation (drug effects)</term><term>Epigenesis, Genetic (drug effects)</term><term>Female</term><term>Gene Expression Regulation, Neoplastic (drug effects)</term><term>HEK293 Cells</term><term>High-Throughput Nucleotide Sequencing</term><term>Humans</term><term>Leukemia, Myelomonocytic, Chronic (drug therapy)</term><term>Leukemia, Myelomonocytic, Chronic (genetics)</term><term>Male</term><term>Middle Aged</term><term>Mutation</term><term>Sequence Analysis, DNA</term><term>Sequence Analysis, RNA</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte d'âge moyen</term><term>Allèles</term><term>Analyse de séquence d'ADN</term><term>Analyse de séquence d'ARN</term><term>Antinéoplasiques antimétabolites (pharmacologie)</term><term>Antinéoplasiques antimétabolites (usage thérapeutique)</term><term>Azacitidine (analogues et dérivés)</term><term>Azacitidine (pharmacologie)</term><term>Azacitidine (usage thérapeutique)</term><term>Cellules HEK293</term><term>Femelle</term><term>Humains</term><term>Leucémie myélomonocytaire chronique (génétique)</term><term>Leucémie myélomonocytaire chronique (traitement médicamenteux)</term><term>Mutation</term><term>Mâle</term><term>Méthylation de l'ADN ()</term><term>Régulation de l'expression des gènes tumoraux ()</term><term>Sujet âgé</term><term>Sujet âgé de 80 ans ou plus</term><term>Survie cellulaire ()</term><term>Séquençage nucléotidique à haut débit</term><term>Épigenèse génétique ()</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Azacitidine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antimetabolites, Antineoplastic</term><term>Azacitidine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antimetabolites, Antineoplastic</term><term>Azacitidine</term></keywords><keywords scheme="MESH" qualifier="analogues et dérivés" xml:lang="fr"><term>Azacitidine</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cell Survival</term><term>DNA Methylation</term><term>Epigenesis, Genetic</term><term>Gene Expression Regulation, Neoplastic</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Leukemia, Myelomonocytic, Chronic</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Leukemia, Myelomonocytic, Chronic</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Leucémie myélomonocytaire chronique</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antinéoplasiques antimétabolites</term><term>Azacitidine</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Leucémie myélomonocytaire chronique</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Antinéoplasiques antimétabolites</term><term>Azacitidine</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Aged, 80 and over</term><term>Alleles</term><term>Female</term><term>HEK293 Cells</term><term>High-Throughput Nucleotide Sequencing</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Mutation</term><term>Sequence Analysis, DNA</term><term>Sequence Analysis, RNA</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte d'âge moyen</term><term>Allèles</term><term>Analyse de séquence d'ADN</term><term>Analyse de séquence d'ARN</term><term>Cellules HEK293</term><term>Femelle</term><term>Humains</term><term>Mutation</term><term>Mâle</term><term>Méthylation de l'ADN</term><term>Régulation de l'expression des gènes tumoraux</term><term>Sujet âgé</term><term>Sujet âgé de 80 ans ou plus</term><term>Survie cellulaire</term><term>Séquençage nucléotidique à haut débit</term><term>Épigenèse génétique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The 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.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Vardiman, J W" uniqKey="Vardiman J">J. W. Vardiman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Padron, E" uniqKey="Padron E">E. Padron</name></author><author><name sortKey="Steensma, D P" uniqKey="Steensma D">D. P. Steensma</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jankowska, A M" uniqKey="Jankowska A">A. M. Jankowska</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Itzykson, R" uniqKey="Itzykson R">R. Itzykson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kon, A" uniqKey="Kon A">A. 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Andrews</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Australie</li><li>France</li><li>Japon</li><li>Royaume-Uni</li><li>États-Unis</li></country></list><tree><country name="France"><noRegion><name sortKey="Merlevede, Jane" sort="Merlevede, Jane" uniqKey="Merlevede J" first="Jane" last="Merlevede">Jane Merlevede</name></noRegion><name sortKey="Artiguenave, Francois" sort="Artiguenave, Francois" uniqKey="Artiguenave F" first="François" last="Artiguenave">François Artiguenave</name><name sortKey="Auboeuf, Didier" sort="Auboeuf, Didier" uniqKey="Auboeuf D" first="Didier" last="Auboeuf">Didier Auboeuf</name><name sortKey="Bernard, Olivier" sort="Bernard, Olivier" uniqKey="Bernard O" first="Olivier" last="Bernard">Olivier Bernard</name><name sortKey="Bernard, Olivier" sort="Bernard, Olivier" uniqKey="Bernard O" first="Olivier" last="Bernard">Olivier Bernard</name><name sortKey="Braun, Thorsten" sort="Braun, Thorsten" uniqKey="Braun T" first="Thorsten" last="Braun">Thorsten Braun</name><name sortKey="Chautard, Emilie" sort="Chautard, Emilie" uniqKey="Chautard E" first="Emilie" last="Chautard">Emilie Chautard</name><name sortKey="Commes, Therese" sort="Commes, Therese" uniqKey="Commes T" first="Thérèse" last="Commes">Thérèse Commes</name><name sortKey="De Botton, Stephane" sort="De Botton, Stephane" uniqKey="De Botton S" first="Stéphane" last="De Botton">Stéphane De Botton</name><name sortKey="De Botton, Stephane" sort="De Botton, Stephane" uniqKey="De Botton S" first="Stéphane" last="De Botton">Stéphane De Botton</name><name sortKey="Deleuze, Jean Francois" sort="Deleuze, Jean Francois" uniqKey="Deleuze J" first="Jean-François" last="Deleuze">Jean-François Deleuze</name><name sortKey="Droin, Nathalie" sort="Droin, Nathalie" uniqKey="Droin N" first="Nathalie" last="Droin">Nathalie Droin</name><name sortKey="Droin, Nathalie" sort="Droin, Nathalie" uniqKey="Droin N" first="Nathalie" last="Droin">Nathalie Droin</name><name sortKey="Droin, Nathalie" sort="Droin, Nathalie" uniqKey="Droin N" first="Nathalie" last="Droin">Nathalie Droin</name><name sortKey="Fenaux, Pierre" sort="Fenaux, Pierre" uniqKey="Fenaux P" first="Pierre" last="Fenaux">Pierre Fenaux</name><name sortKey="Itzykson, Raphael" sort="Itzykson, Raphael" uniqKey="Itzykson R" first="Raphael" last="Itzykson">Raphael Itzykson</name><name sortKey="Jourdan, Eric" sort="Jourdan, Eric" uniqKey="Jourdan E" first="Eric" last="Jourdan">Eric Jourdan</name><name sortKey="Koscielny, Serge" sort="Koscielny, Serge" uniqKey="Koscielny S" first="Serge" last="Koscielny">Serge Koscielny</name><name sortKey="Merlevede, Jane" sort="Merlevede, Jane" uniqKey="Merlevede J" first="Jane" last="Merlevede">Jane Merlevede</name><name sortKey="Meyer, Vincent" sort="Meyer, Vincent" uniqKey="Meyer V" first="Vincent" last="Meyer">Vincent Meyer</name><name sortKey="Morabito, Margot" sort="Morabito, Margot" uniqKey="Morabito M" first="Margot" last="Morabito">Margot Morabito</name><name sortKey="Morabito, Margot" sort="Morabito, Margot" uniqKey="Morabito M" first="Margot" last="Morabito">Margot Morabito</name><name sortKey="Pata Merci, Noemie" sort="Pata Merci, Noemie" uniqKey="Pata Merci N" first="Noemie" last="Pata-Merci">Noemie Pata-Merci</name><name sortKey="Preudhomme, Claude" sort="Preudhomme, Claude" uniqKey="Preudhomme C" first="Claude" last="Preudhomme">Claude Preudhomme</name><name sortKey="Quesnel, Bruno" sort="Quesnel, Bruno" uniqKey="Quesnel B" first="Bruno" last="Quesnel">Bruno Quesnel</name><name sortKey="Selimoglu Buet, Dorothee" sort="Selimoglu Buet, Dorothee" uniqKey="Selimoglu Buet D" first="Dorothée" last="Selimoglu-Buet">Dorothée Selimoglu-Buet</name><name sortKey="Selimoglu Buet, Dorothee" sort="Selimoglu Buet, Dorothee" uniqKey="Selimoglu Buet D" first="Dorothée" last="Selimoglu-Buet">Dorothée Selimoglu-Buet</name><name sortKey="Solary, Eric" sort="Solary, Eric" uniqKey="Solary E" first="Eric" last="Solary">Eric Solary</name><name sortKey="Solary, Eric" sort="Solary, Eric" uniqKey="Solary E" first="Eric" last="Solary">Eric Solary</name><name sortKey="Solary, Eric" sort="Solary, Eric" uniqKey="Solary E" first="Eric" last="Solary">Eric Solary</name><name sortKey="Solier, Stephanie" sort="Solier, Stephanie" uniqKey="Solier S" first="Stéphanie" last="Solier">Stéphanie Solier</name><name sortKey="Solier, Stephanie" sort="Solier, Stephanie" uniqKey="Solier S" first="Stéphanie" last="Solier">Stéphanie Solier</name><name sortKey="Vainchenker, William" sort="Vainchenker, William" uniqKey="Vainchenker W" first="William" last="Vainchenker">William Vainchenker</name><name sortKey="Vainchenker, William" sort="Vainchenker, William" uniqKey="Vainchenker W" first="William" last="Vainchenker">William Vainchenker</name></country><country name="États-Unis"><noRegion><name sortKey="Qin, Tingting" sort="Qin, Tingting" uniqKey="Qin T" first="Tingting" last="Qin">Tingting Qin</name></noRegion><name sortKey="Alexandrov, Ludmil B" sort="Alexandrov, Ludmil B" uniqKey="Alexandrov L" first="Ludmil B." last="Alexandrov">Ludmil B. Alexandrov</name><name sortKey="Alexandrov, Ludmil B" sort="Alexandrov, Ludmil B" uniqKey="Alexandrov L" first="Ludmil B." last="Alexandrov">Ludmil B. Alexandrov</name><name sortKey="Figueroa, Maria" sort="Figueroa, Maria" uniqKey="Figueroa M" first="Maria" last="Figueroa">Maria Figueroa</name><name sortKey="Meldi, Kristen" sort="Meldi, Kristen" uniqKey="Meldi K" first="Kristen" last="Meldi">Kristen Meldi</name><name sortKey="Padron, Eric" sort="Padron, Eric" uniqKey="Padron E" first="Eric" last="Padron">Eric Padron</name></country><country name="Japon"><noRegion><name sortKey="Yoshida, Kenichi" sort="Yoshida, Kenichi" uniqKey="Yoshida K" first="Kenichi" last="Yoshida">Kenichi Yoshida</name></noRegion><name sortKey="Ogawa, Seishi" sort="Ogawa, Seishi" uniqKey="Ogawa S" first="Seishi" last="Ogawa">Seishi Ogawa</name></country><country name="Australie"><noRegion><name sortKey="Gayevskiy, Velimir" sort="Gayevskiy, Velimir" uniqKey="Gayevskiy V" first="Velimir" last="Gayevskiy">Velimir Gayevskiy</name></noRegion><name sortKey="Cowley, Mark J" sort="Cowley, Mark J" uniqKey="Cowley M" first="Mark J." last="Cowley">Mark J. Cowley</name><name sortKey="Dinger, Marcel E" sort="Dinger, Marcel E" uniqKey="Dinger M" first="Marcel E." last="Dinger">Marcel E. Dinger</name></country><country name="Royaume-Uni"><noRegion><name sortKey="Stratton, Michael R" sort="Stratton, Michael R" uniqKey="Stratton M" first="Michael R." last="Stratton">Michael R. Stratton</name></noRegion><name sortKey="Alexandrov, Ludmil B" sort="Alexandrov, Ludmil B" uniqKey="Alexandrov L" first="Ludmil B." last="Alexandrov">Ludmil B. Alexandrov</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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