Nov 27, 2014

Age-related clonal hematopoiesis associated with adverse outcomes

The New England Journal of Medicine
Siddhartha JaiswalBenjamin L Ebert

Abstract

The incidence of hematologic cancers increases with age. These cancers are associated with recurrent somatic mutations in specific genes. We hypothesized that such mutations would be detectable in the blood of some persons who are not known to have hematologic disorders. We analyzed whole-exome sequencing data from DNA in the peripheral-blood cells of 17,182 persons who were unselected for hematologic phenotypes. We looked for somatic mutations by identifying previously characterized single-nucleotide variants and small insertions or deletions in 160 genes that are recurrently mutated in hematologic cancers. The presence of mutations was analyzed for an association with hematologic phenotypes, survival, and cardiovascular events. Detectable somatic mutations were rare in persons younger than 40 years of age but rose appreciably in frequency with age. Among persons 70 to 79 years of age, 80 to 89 years of age, and 90 to 108 years of age, these clonal mutations were observed in 9.5% (219 of 2300 persons), 11.7% (37 of 317), and 18.4% (19 of 103), respectively. The majority of the variants occurred in three genes: DNMT3A, TET2, and ASXL1. The presence of a somatic mutation was associated with an increase in the risk of hematologic...Continue Reading

  • References43
  • Citations651

References

Mentioned in this Paper

Ischemic Cerebrovascular Accident
Diabetes Mellitus, Non-Insulin-Dependent
Meta-Analysis (Publications)
Hematology (Discipline)
Colony-Forming Units, Hematopoietic
Hematologic Neoplasms
Exons
Somatic Mutation
Murine
Monoclonal Gammopathy of Undetermined Significance

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