Leukemia-Associated Somatic Mutations Drive Distinct Patterns of Age-Related Clonal Hemopoiesis

• DOI: 10.1016/j.celrep.2015.02.005
• Publication Date: 2015-02-26T12:46:42Z
• Authors: Thomas McKerrell; Naomi Park; Thaidy Moreno; Carolyn S. Grove; Hannes Ponstingl; Jonathan Stephens; Charles Crawley; Jenny Craig; Mike A. Scott; Clare Hodkinson; Joanna Baxter; Roland Rad; Duncan R. Forsyth; Michael A. Quail; Eleftheria Zeggini; Willem Ouwehand; Ignacio Varela; George S. Vassiliou
• Keywords: Spliceosome

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 DNA from 4,219 individuals using ultra-deep sequencing. Using only the studied, identified clonal 0.8% under 60, rising to 19.5% those ≥90 years, thus predicting that is much more prevalent than previously realized. DNMT3A-R882 were most common and, although their prevalence increased with age, found as young 25 years. By contrast, affecting spliceosome genes SF3B1 and SRSF2, closely associated myelodysplastic syndromes, aged >70 several harboring one such mutation. This indicates drive expansion selection pressures particular aging hemopoietic system explains high incidence disorders these advanced old age.