This survey is the first large-scale study of acquired chromosomal anomalies in people of all ages and various states of health. Previously, the extent of chromosomal variation within developmentally normal individuals, in the absence of overt cancer, was largely unknown. The results presented here indicate that a significant fraction of blood cells in people without a prior history of hematological cancer may contain large chromosomal anomalies, including multi-megabase deletions, duplications and aUPD. The frequency of people with such clonal anomalies in a mosaic state is low up to about 50 years of age and then increases rapidly up to 2–3%. We find that these anomalies are associated with an approximately ten-fold higher risk of hematological cancer, but subjects with detectable clonal mosaicism may survive for years without having a hematological cancer diagnosis. Further work is needed to determine the stability of the mosaic state over time, to replicate and improve estimates of the predisposition to hematological cancer, and to identify anomalies associated with asymptomatic cancer precursor conditions. It also will be important to explore the health consequences of these anomalies for conditions other than cancer, such as immune system function.
