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Nat Commun. 2016 Dec 16;7:13765. doi: 10.1038/ncomms13765.

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

Author information

1
BGI-Shenzhen, Shenzhen 518083, China.
2
State Key Laboratory of Bioelectronics, Southeast University, Nanjing 210096, China.
3
School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China.
4
Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland 20892, USA.
5
School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, China.
6
Cancer Genomics Research Laboratory, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Leidos Biomedical Research Inc., Bethesda, Maryland 20892, USA.
7
BGI-Education Center, University of Chinese Academy of Sciences, Shenzhen 518083, China.
8
Biomatrix, Bethesda, Maryland 20849, USA.
9
Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, Maryland 20993, USA.
10
Department of Biology, University of Copenhagen, Copenhagen 1599, Denmark.
11
James D. Watson Institute of Genome Sciences, Hangzhou 310058, China.

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.

PMID:
27982015
PMCID:
PMC5171825
DOI:
10.1038/ncomms13765
[Indexed for MEDLINE]
Free PMC Article

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