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Nat Commun. 2016 Aug 22;7:12484. doi: 10.1038/ncomms12484.

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

Author information

1
Department of Pediatrics, Division of Hematology and Oncology, Washington University School of Medicine, Saint Louis, Missouri 63108, USA.
2
Center for Genome Sciences and Systems Biology, Washington University School of Medicine, Saint Louis, Missouri 63108, USA.
3
Department of Internal Medicine, Division of Oncology, Washington University School of Medicine, Saint Louis, Missouri 63108, USA.
4
Department of Medicine, Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.

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.

PMID:
27546487
PMCID:
PMC4996934
DOI:
10.1038/ncomms12484
[Indexed for MEDLINE]
Free PMC Article

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