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Clonal evolution in myelodysplastic syndromes

Author

Listed:
  • Pedro da Silva-Coelho

    (Laboratory of Hematology, Radboud University Medical Center
    Centro Hospitalar de São João and Faculdade de Medicina da Universidade do Porto, Alameda Professor Hernâni Monteiro)

  • 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
    University Medical Centre Groningen)

  • 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)

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.

Suggested Citation

  • 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 & Ma, 2017. "Clonal evolution in myelodysplastic syndromes," Nature Communications, Nature, vol. 8(1), pages 1-11, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15099
    DOI: 10.1038/ncomms15099
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