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Clonal haematopoiesis harbouring AML-associated mutations is ubiquitous in healthy adults

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  • Andrew L. Young

    (Washington University School of Medicine
    Center for Genome Sciences and Systems Biology, Washington University School of Medicine)

  • Grant A. Challen

    (Washington University School of Medicine)

  • Brenda M. Birmann

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Todd E. Druley

    (Washington University School of Medicine
    Center for Genome Sciences and Systems Biology, Washington University School of Medicine)

Abstract

Clonal haematopoiesis is thought to be a rare condition that increases in frequency with age and predisposes individuals to haematological malignancy. Recent studies, utilizing next-generation sequencing (NGS), observed haematopoietic clones in 10% of 70-year olds and rarely in younger individuals. However, these studies could only detect common haematopoietic clones—>0.02 variant allele fraction (VAF)—due to the error rate of NGS. To identify and characterize clonal mutations below this threshold, here we develop methods for targeted error-corrected sequencing, which enable the accurate detection of clonal mutations as rare as 0.0003 VAF. We apply these methods to study serially banked peripheral blood samples from healthy 50–60-year-old participants in the Nurses’ Health Study. We observe clonal haematopoiesis, frequently harbouring mutations in DNMT3A and TET2, in 95% of individuals studied. These clonal mutations are often stable longitudinally and present in multiple haematopoietic compartments, suggesting a long-lived haematopoietic stem and progenitor cell of origin.

Suggested Citation

  • Andrew L. Young & Grant A. Challen & Brenda M. Birmann & Todd E. Druley, 2016. "Clonal haematopoiesis harbouring AML-associated mutations is ubiquitous in healthy adults," Nature Communications, Nature, vol. 7(1), pages 1-7, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12484
    DOI: 10.1038/ncomms12484
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    Cited by:

    1. Oriol Pich & Iker Reyes-Salazar & Abel Gonzalez-Perez & Nuria Lopez-Bigas, 2022. "Discovering the drivers of clonal hematopoiesis," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Peng Dai & Lucia Ruojia Wu & Sherry Xi Chen & Michael Xiangjiang Wang & Lauren Yuxuan Cheng & Jinny Xuemeng Zhang & Pengying Hao & Weijie Yao & Jabra Zarka & Ghayas C. Issa & Lawrence Kwong & David Yu, 2021. "Calibration-free NGS quantitation of mutations below 0.01% VAF," Nature Communications, Nature, vol. 12(1), pages 1-9, December.

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