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タイトル: | Mutation allele burden remains unchanged in chronic myelomonocytic leukaemia responding to hypomethylating agents |
著者: | Merlevede, Jane Droin, Nathalie Qin, Tingting Meldi, Kristen Yoshida, Kenichi Morabito, Margot Chautard, Emilie Auboeuf, Didier Fenaux, Pierre Braun, Thorsten Itzykson, Raphael De Botton, Stéphane Quesnel, Bruno Commes, Thérèse Jourdan, Eric Vainchenker, William Bernard, Olivier Pata-Merci, Noemie Solier, Stéphanie Gayevskiy, Velimir Dinger, Marcel E. Cowley, Mark J. Selimoglu-Buet, Dorothée Meyer, Vincent Artiguenave, François Deleuze, Jean François Preudhomme, Claude Stratton, Michael R. Alexandrov, Ludmil B. Padron, Eric Ogawa, Seishi Koscielny, Serge Figueroa, Maria Solary, Eric |
著者名の別形: | 小川, 誠司 |
キーワード: | Biological sciences Cancer Genetics |
発行日: | 24-Feb-2016 |
出版者: | Nature Publishing Group |
誌名: | Nature Communications |
巻: | 7 |
論文番号: | 10767 |
抄録: | 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. |
著作権等: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
URI: | http://hdl.handle.net/2433/210212 |
DOI(出版社版): | 10.1038/ncomms10767 |
PubMed ID: | 26908133 |
出現コレクション: | 学術雑誌掲載論文等 |
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