Clonal haematopoiesis harbouring AML-associated mutations is ubiquitous in healthy adults
By A. Young, Grant A. Challen, Brenda M. Birmann, T. Druley. Nature Communications, 2016
640 citations recorded by the source corpus.
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. Clonal haematopoiesis has been thought to occur in less than 10% of individuals younger than 70 years old. Here, the authors use an error corrected next-generation sequencing method to find clonal haematopoiesis in the peripheral blood of 19 of 20 healthy 50–70 year old individuals.
Subfields: Cancer Research, Genetics, Hematology
View Paper: https://www.semanticscholar.org/paper/9259ca9fc112d0c8a7eef43acd7aede6fb0f8531
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Citations in the corpus
- Tet2-mediated Clonal Hematopoiesis Accelerates Heart Failure through a Mechanism Involving the IL-1β/NLRP3 Inflammasome (2018, background): “Remarkably, a study employing highly sensitive targeted error-corrected sequencing revealed that 95% of individuals in their 50’s possesses low levels of these mutations (predominantly DNMT3A and TET2), suggesting that the seeding of bone marrow with mutated hematopoietic cells is essentially ubiqui”
- Clonal hematopoiesis in human aging and disease (2019, neutral): “Some people have clones that remain stagnant in size for many years, whereas other people have clones that show steady growth (29, 34).”
- Therapy-related clonal hematopoiesis in patients with non-hematologic cancers is common and impacts clinical outcome (2017, background): “…from healthy subjects identified somatic mutations in leukemia-associated genes, most commonly in DNMT3A, TET2, and ASXL1, in asymptomatic individuals without known hematologic disease (Genovese et al., 2014; Jaiswal et al., 2014; McKerrell et al., 2015; Xie et al., 2014; Young et al., 2016).”