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Evolutionary landscape of clonal hematopoiesis in 3,359 individuals from the general population

van Zeventer, Isabelle A., de Graaf, Aniek O., Salzbrunn, Jonas B., Nolte, Ilja M., Kamphuis, Priscilla, Dinmohamed, Avinash, van der Reijden, Bert A., Schuringa, Jan Jacob, Jansen, Joop H., Huls, Gerwin·2023·Cancer Cell
DOI 10.1016/j.ccell.2023.04.006
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Abstract

Knowledge about evolution of clonal hematopoiesis, which may drive malignant progression, is crucial for clinical decision-making. We investigated the landscape of clonal evolution by error-corrected sequencing on 7,045 sequential samples from 3,359 individuals in the prospective population-based Lifelines cohort, with a special focus on cytosis and cytopenia. Spliceosome (SRSF2/U2AF1/SF3B1) and JAK2 mutated clones show highest growth rates over a median 3.6-year period, while clone sizes for DNMT3A and TP53 increase only marginally, independent of cytosis or cytopenia. Nevertheless, large differences are observed between individuals carrying the same mutation, indicative of modulation by non-mutation-related factors. Clonal expansion is not dependent on classical cancer risk factors (e.g., smoking). Risk for incident myeloid malignancy diagnosis is highest for JAK2, spliceosome, or TP53 mutations and absent for DNMT3A, and it is mostly preceded by cytosis or cytopenia. The results provide important insight into high-risk evolutionary patterns to guide monitoring of "CHIP" and "CCUS."

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Metadata

Authors
van Zeventer, I. A., de Graaf, A. O., Salzbrunn, J. B., Nolte, I. M., Kamphuis, P., Dinmohamed, A., van der Reijden, B. A., Schuringa, J. J., Jansen, J. H., & Huls, G.
Venue
Cancer Cell
Publisher
Elsevier BV
Published
2023-06
Volume
41
Issue
6
Pages
1017-1031.e4
ISSN
1535-6108
DOI
10.1016/j.ccell.2023.04.006
Cited by
91
References
23
Language
en
Licence
Funders
  • European Union
  • Rijksuniversiteit Groningen
  • Horizon 2020 Framework Programme
  • Ministerie van Volksgezondheid, Welzijn en Sport
  • Ministerie van Economische Zaken
  • Horizon 2020 (634789)
  • Stanford Genome Technology Center

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CoChat. (2026). Citation check: Evolutionary landscape of clonal hematopoiesis in 3,359 individuals from the general population. https://app.cochat.ai/papers/10.1016/j.ccell.2023.04.006
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van Zeventer, I. A., de Graaf, A. O., Salzbrunn, J. B., Nolte, I. M., Kamphuis, P., Dinmohamed, A., van der Reijden, B. A., Schuringa, J. J., Jansen, J. H., & Huls, G. (2023). Evolutionary landscape of clonal hematopoiesis in 3,359 individuals from the general population. Cancer Cell. https://doi.org/10.1016/j.ccell.2023.04.006