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

Andrew L. Young, Grant A. Challen, Brenda M. Birmann and Todd E. Druley ()
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Andrew L. Young: 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

Nature Communications, 2016, vol. 7, issue 1, 1-7

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms12484

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