decline in replicative function35 could result in a decrease in the effective population size of stem cells, leading to shifts in clonal composition analogous to random drift in small populations of individuals36. However, analyses of the clonal composition of blood cells, based on X-inactivation markers in healthy women, suggest stability over time and between lymphoid and myeloid lineages, even in the elderly37,38. Therefore, in most cases, positive selection may be required to establish clones of cells with chromosomal anomalies that are sufficiently large for detection with SNP microarrays. The potential for positive selection may increase with age as somatic mutations accumulate in genes that regulate cellular proliferation. For example, a highly proliferative clone may arise when a recessive tumor suppressor mutation becomes hemizygous in combination with a deletion, or homozygous due to aUPD. This suggestion is supported by the observation that acquired anomalies tend to cluster in certain genomic regions and that common deleted regions pinpoint genes previously associated with hematological cancer.
