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Evolution of multiple cell clones over a 29-year period of a CLL patient

Author

Listed:
  • Zhikun Zhao

    (BGI-Shenzhen
    State Key Laboratory of Bioelectronics, Southeast University
    School of Biological Science and Medical Engineering, Southeast University)

  • Lynn Goldin

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Shiping Liu

    (BGI-Shenzhen
    School of Life Sciences, Sun Yat-sen University)

  • Liang Wu

    (BGI-Shenzhen)

  • Weiyin Zhou

    (Cancer Genomics Research Laboratory, National Cancer Institute, Leidos Biomedical Research Inc.)

  • Hong Lou

    (Cancer Genomics Research Laboratory, National Cancer Institute, Leidos Biomedical Research Inc.)

  • Qichao Yu

    (BGI-Shenzhen
    BGI-Education Center, University of Chinese Academy of Sciences)

  • Shirley X. Tsang

    (Biomatrix)

  • Miaomiao Jiang

    (BGI-Shenzhen
    School of Biological Science and Medical Engineering, Southeast University)

  • Fuqiang Li

    (BGI-Shenzhen)

  • MaryLou McMaster

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Yang Li

    (BGI-Shenzhen)

  • Xinxin Lin

    (BGI-Shenzhen)

  • Zhifeng Wang

    (BGI-Shenzhen)

  • Liqin Xu

    (BGI-Shenzhen)

  • Gerald Marti

    (Center for Devices and Radiological Health, Food and Drug Administration)

  • Guibo Li

    (BGI-Shenzhen
    University of Copenhagen)

  • Kui Wu

    (BGI-Shenzhen
    University of Copenhagen)

  • Meredith Yeager

    (Cancer Genomics Research Laboratory, National Cancer Institute, Leidos Biomedical Research Inc.)

  • Huanming Yang

    (BGI-Shenzhen
    James D. Watson Institute of Genome Sciences)

  • Xun Xu

    (BGI-Shenzhen)

  • Stephen J. Chanock

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Bo Li

    (BGI-Shenzhen)

  • Yong Hou

    (BGI-Shenzhen
    University of Copenhagen)

  • Neil Caporaso

    (National Cancer Institute (NCI), National Institutes of Health (NIH))

  • Michael Dean

    (BGI-Shenzhen
    National Cancer Institute (NCI), National Institutes of Health (NIH))

Abstract

Chronic lymphocytic leukaemia (CLL) is a frequent B-cell malignancy, characterized by recurrent somatic chromosome alterations and a low level of point mutations. Here we present single-nucleotide polymorphism microarray analyses of a single CLL patient over 29 years of observation and treatment, and transcriptome and whole-genome sequencing at selected time points. We identify chromosome alterations 13q14−, 6q− and 12q+ in early cell clones, elimination of clonal populations following therapy, and subsequent appearance of a clone containing trisomy 12 and chromosome 10 copy-neutral loss of heterogeneity that marks a major population dominant at death. Serial single-cell RNA sequencing reveals an expression pattern with high FOS, JUN and KLF4 at disease acceleration, which resolves following therapy, but reoccurs following relapse and death. Transcriptome evolution indicates complex changes in expression occur over time. In conclusion, CLL can evolve gradually during indolent phases, and undergo rapid changes following therapy.

Suggested Citation

  • Zhikun Zhao & Lynn Goldin & Shiping Liu & Liang Wu & Weiyin Zhou & Hong Lou & Qichao Yu & Shirley X. Tsang & Miaomiao Jiang & Fuqiang Li & MaryLou McMaster & Yang Li & Xinxin Lin & Zhifeng Wang & Liqi, 2016. "Evolution of multiple cell clones over a 29-year period of a CLL patient," Nature Communications, Nature, vol. 7(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13765
    DOI: 10.1038/ncomms13765
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