Mosaicism is defined as the coexistence of cells with different genetic composition within an individual, caused by postzygotic somatic mutation. Although somatic mosaicism for chromosomal abnormalities is a well-established cause of developmental and somatic disorders and has also been detected in different tissues, its frequency and extent in the adult normal population are still unknown. We provide here a genome-wide survey of mosaic genomic variation obtained by analyzing Illumina 1M SNP array data from blood or buccal DNA samples of 1991 adult individuals from the Spanish Bladder Cancer/EPICURO genome-wide association study. We found mosaic abnormalities in autosomes in 1.7% of samples, including 23 segmental uniparental disomies, 8 complete trisomies, and 11 large (1.5-37 Mb) copy-number variants. Alterations were observed across the different autosomes with recurrent events in chromosomes 9 and 20. No case-control differences were found in the frequency of events or the percentage of cells affected, thus indicating that most rearrangements found are not central to the development of bladder cancer. However, five out of six events tested were detected in both blood and bladder tissue from the same individual, indicating an early developmental origin. The high cellular frequency of the anomalies detected and their presence in normal adult individuals suggest that this type of mosaicism is a widespread phenomenon in the human genome. Somatic mosaicism should be considered in the expanding repertoire of inter- and intraindividual genetic variation, some of which may cause somatic human diseases but also contribute to modifying inherited disorders and/or late-onset multifactorial traits.

This work was supported by the Intramural Research Program of the NCI Division of Cancer Epidemiology and Genetics (to N.R., D.S., and S.J.C.), the Asociación Española Contra el Cáncer (to F.X.R., N.M., and L.A.P.-J.), EU-6FP grants LSHG-CT-2006-037627 (to L.A.P.-J.) and HEALTH-STREP-2006-037739-DropTop (to N.M. and F.X.R.), Fondo de Investigación Sanitaria grants PI076832 (to L.A.P.-J.) and PI061614 (to F.X.R.), Consolider ONCOBIO (to F.X.R.), National Institutes of Health grant R01 CA089715-06A2 (to N.M. and F.X.R.), Red Temática de Investigación Cooperativa en Cáncer (to N.M. and A.C.), Fundació La Marató de TV3 (to N.M.), and EU-7FP grant agreements #201663-UROMOL (to N.M. and F.X.R.) and #201333-DEC-anBIO(to N.M.). B.R.-S. and G.M.were supportedby a postdoctoral fellowship (FIS CD06/00019) and a predoctoral fellowship (FI09/00205) of the Fondo Investigación Sanitaria, respectively.