Clonal evolution in myelodysplastic syndromes

Pedro da Silva-Coelho, Leonie I. Kroeze, Kenichi Yoshida, Theresia N. Koorenhof-Scheele, Ruth Knops, Louis T. van de Locht, Aniek O. de Graaf, Marion Massop, Sarah Sandmann, Martin Dugas, Marian J. Stevens-Kroef, Jaroslav Cermak, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Theo de Witte, Nicole M. A. Blijlevens, Petra Muus, Gerwin Huls, Bert A. van der Reijden, Seishi Ogawa () and Joop H. Jansen ()
Additional contact information
Pedro da Silva-Coelho: Laboratory of Hematology, Radboud University Medical Center
Leonie I. Kroeze: Laboratory of Hematology, Radboud University Medical Center
Kenichi Yoshida: Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto-shi
Theresia N. Koorenhof-Scheele: Laboratory of Hematology, Radboud University Medical Center
Ruth Knops: Laboratory of Hematology, Radboud University Medical Center
Louis T. van de Locht: Laboratory of Hematology, Radboud University Medical Center
Aniek O. de Graaf: Laboratory of Hematology, Radboud University Medical Center
Marion Massop: Laboratory of Hematology, Radboud University Medical Center
Sarah Sandmann: Institute of Medical Informatics, University of Münster
Martin Dugas: Institute of Medical Informatics, University of Münster
Marian J. Stevens-Kroef: Radboud University Medical Center
Jaroslav Cermak: Institute of Hematology and Blood Transfusion
Yuichi Shiraishi: Human Genome Center, Institute of Medical Science, The University of Tokyo
Kenichi Chiba: Human Genome Center, Institute of Medical Science, The University of Tokyo
Hiroko Tanaka: Human Genome Center, Institute of Medical Science, The University of Tokyo
Satoru Miyano: Human Genome Center, Institute of Medical Science, The University of Tokyo
Theo de Witte: Radboud University Medical Center, Radboud Institute for Molecular Life Sciences
Nicole M. A. Blijlevens: Radboud University Medical Center
Petra Muus: Radboud University Medical Center
Gerwin Huls: Radboud University Medical Center
Bert A. van der Reijden: Laboratory of Hematology, Radboud University Medical Center
Seishi Ogawa: Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto-shi
Joop H. Jansen: Laboratory of Hematology, Radboud University Medical Center

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: Abstract Cancer development is a dynamic process during which the successive accumulation of mutations results in cells with increasingly malignant characteristics. Here, we show the clonal evolution pattern in myelodysplastic syndrome (MDS) patients receiving supportive care, with or without lenalidomide (follow-up 2.5–11 years). Whole-exome and targeted deep sequencing at multiple time points during the disease course reveals that both linear and branched evolutionary patterns occur with and without disease-modifying treatment. The application of disease-modifying therapy may create an evolutionary bottleneck after which more complex MDS, but also unrelated clones of haematopoietic cells, may emerge. In addition, subclones that acquired an additional mutation associated with treatment resistance (TP53) or disease progression (NRAS, KRAS) may be detected months before clinical changes become apparent. Monitoring the genetic landscape during the disease may help to guide treatment decisions.

Date: 2017
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DOI: 10.1038/ncomms15099

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