Journal
CELL REPORTS
Volume 10, Issue 8, Pages 1239-1245Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2015.02.005
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Funding
- Wellcome Trust Clinician Scientist Fellowship [100678/Z/12/Z]
- Wellcome Trust Sanger Institute [WT098051]
- Wellcome Trust Senior Fellowship in Clinical Science [WT095663MA]
- Leukaemia Lymphoma Research
- Kay Kendal Leukaemia Fund
- Spanish Ministerio de Economia y Competitividad subprograma Ramon y Cajal
- Leukaemia Lymphoma Research Clinical Research Training Fellowship
- Servicio Santander Supercomputacion
- Wellcome Trust [076113/C/04/Z]
- Juvenile Diabetes Research Foundation grant [WT061858]
- National Institute of Health Research of England
- Economic and Social Research Council, UK
- Celgene
- British Heart Foundation [RG/09/012/28096] Funding Source: researchfish
- Economic and Social Research Council [ES/H029745/1] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0513-10151, NF-SI-0510-10214, RP-PG-0310-1002] Funding Source: researchfish
- ESRC [ES/H029745/1] Funding Source: UKRI
- Wellcome Trust [100678/Z/12/Z] Funding Source: Wellcome Trust
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Clonal hemopoiesis driven by leukemia-associated gene mutations can occur without evidence of a blood disorder. To investigate this phenomenon, we interrogated 15 mutation hot spots in blood DNA from 4,219 individuals using ultra-deep sequencing. Using only the hot spots studied, we identified clonal hemopoiesis in 0.8% of individuals under 60, rising to 19.5% of those >= 90 years, thus predicting that clonal hemopoiesis is much more prevalent than previously realized. DNMT3A-R882 mutations were most common and, although their prevalence increased with age, were found in individuals as young as 25 years. By contrast, mutations affecting spliceosome genes SF3B1 and SRSF2, closely associated with the myelodysplastic syndromes, were identified only in those aged > 70 years, with several individuals harboring more than one such mutation. This indicates that spliceosome gene mutations drive clonal expansion under selection pressures particular to the aging hemopoietic system and explains the high incidence of clonal disorders associated with these mutations in advanced old age.
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