Detectable clonal mosaicism from birth to old age and its relationship to cancer

Nat Genet. 2012 May 6;44(6):642-50. doi: 10.1038/ng.2271.

Abstract

We detected clonal mosaicism for large chromosomal anomalies (duplications, deletions and uniparental disomy) using SNP microarray data from over 50,000 subjects recruited for genome-wide association studies. This detection method requires a relatively high frequency of cells with the same abnormal karyotype (>5-10%; presumably of clonal origin) in the presence of normal cells. The frequency of detectable clonal mosaicism in peripheral blood is low (<0.5%) from birth until 50 years of age, after which it rapidly rises to 2-3% in the elderly. Many of the mosaic anomalies are characteristic of those found in hematological cancers and identify common deleted regions with genes previously associated with these cancers. Although only 3% of subjects with detectable clonal mosaicism had any record of hematological cancer before DNA sampling, those without a previous diagnosis have an estimated tenfold higher risk of a subsequent hematological cancer (95% confidence interval = 6-18).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / genetics*
  • Child
  • Child, Preschool
  • Chromosome Aberrations*
  • Chromosome Mapping
  • DNA Copy Number Variations
  • Female
  • Genome-Wide Association Study
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • Mosaicism*
  • Neoplasms / genetics*

Grant support