@article{3ebdb6f9357d4f09a37ec287e3d2b85c,
title = "Evolutionary landscape of clonal hematopoiesis in 3,359 individuals from the general population",
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.”",
keywords = "CHIP, clonal evolution, clonal hematopoiesis, Cytopenia, cytosis, elderly, somatic mutations",
author = "{van Zeventer}, {Isabelle A.} and {de Graaf}, {Aniek O.} and Salzbrunn, {Jonas B.} and Nolte, {Ilja M.} and Priscilla Kamphuis and Avinash Dinmohamed and {van der Reijden}, {Bert A.} and Schuringa, {Jan Jacob} and Jansen, {Joop H.} and Gerwin Huls",
note = "Funding Information: The Lifelines Biobank initiative has been made possible by subsidy from the Dutch Ministry of Health, Welfare and Sport, the Dutch Ministry of Economic Affairs, the University Medical Center Groningen (UMCG the Netherlands), University Groningen, and the Northern Provinces of the Netherlands. The authors would like to thank all participants of the Lifelines cohort study and everybody contributing to the study setup and design. This work is part of the MDS-RIGHT project, which has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 634789, “Providing the right care to the right patient with myelodysplastic syndrome at the right time.” The authors would also like to thank all local investigators and operational team members of the MDS-RIGHT project for their contribution. The authors thank the registration team of the Netherlands Comprehensive Cancer Organisation (IKNL) for the collection of data for the Netherlands Cancer Registry as well as IKNL staff for scientific advice. Finally, we thank the Genome Technology Center, Radboud University Medical Center, for performing NovaSeq sequencing. Conceptualization and methodology, I.A.v.Z. A.O.d.G. J.H.J. and G.H.; resources, A.D. J.J.S. J.H.J. and G.H.; data curation, I.A.v.Z. A.O.d.G. J.B.S. and P.K.; (statistical) analysis, I.A.v.Z. and I.M.N.; investigation, I.A.v.Z. A.O.d.G. and J.B.S.; writing – original draft, I.A.v.Z. and G.H.; writing – review & editing, A.O.d.G. J.B.S. P.K. B.A.v.d.R. A.D. J.J.S. and J.H.J.; funding acquisition and supervision, J.H.J. and G.H. The authors declare to have no competing interests. We support inclusive, diverse, and equitable conduct of research. Funding Information: The Lifelines Biobank initiative has been made possible by subsidy from the Dutch Ministry of Health, Welfare and Sport, the Dutch Ministry of Economic Affairs, the University Medical Center Groningen (UMCG the Netherlands), University Groningen, and the Northern Provinces of the Netherlands. The authors would like to thank all participants of the Lifelines cohort study and everybody contributing to the study setup and design. This work is part of the MDS-RIGHT project, which has received funding from the European Union{\textquoteright}s Horizon 2020 research and innovation program under grant agreement No 634789 , “Providing the right care to the right patient with myelodysplastic syndrome at the right time.” The authors would also like to thank all local investigators and operational team members of the MDS-RIGHT project for their contribution. The authors thank the registration team of the Netherlands Comprehensive Cancer Organisation (IKNL) for the collection of data for the Netherlands Cancer Registry as well as IKNL staff for scientific advice. Finally, we thank the Genome Technology Center, Radboud University Medical Center, for performing NovaSeq sequencing. Publisher Copyright: {\textcopyright} 2023 Elsevier Inc.",
year = "2023",
month = jun,
day = "12",
doi = "10.1016/j.ccell.2023.04.006",
language = "English",
volume = "41",
pages = "1017--1031.e4",
journal = "Cancer cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "6",
}