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

CC Laurie, CA Laurie, K Rice, KF Doheny, LR Zelnick… - Nature …, 2012 - nature.com
CC Laurie, CA Laurie, K Rice, KF Doheny, LR Zelnick, CP McHugh, H Ling, KN Hetrick…
Nature genetics, 2012nature.com
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 …
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).
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