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

• DOI: 10.1038/ng.2271
• Publication Date: 2012-05-06T17:18:54Z
• Authors: Cathy C Laurie; Cecelia A Laurie; Kenneth Rice; Kimberly F Doheny; Leila R Zelnick; Caitlin P McHugh; Hua Ling; Kurt N Hetrick; Elizabeth W Pugh; Chris Amos; Qingyi Wei; Li-e Wang; Jeffrey E Lee; Kathleen C Barnes; Nadia N Hansel; Rasika Mathias; Denise Daley; Terri H Beaty; Alan F Scott; Ingo Ruczinski; Rob B Scharpf; Laura J Bierut; Sarah M Hartz; Maria Teresa Landi; Neal D Freedman; Lynn R Goldin; David Ginsburg; Jun Li; Karl C Desch; Sara S Strom; William J Blot; Lisa B Signorello; Sue A Ingles; Stephen J Chanock; Sonja I Berndt; Loic Le Marchand; Brian E Henderson; Kristine R Monroe; John A Heit; Mariza de Andrade; Sebastian M Armasu; Cynthia Regnier; William L Lowe; M Geoffrey Hayes; Mary L Marazita; Eleanor Feingold; Jeffrey C Murray; Mads Melbye; Bjarke Feenstra; Jae H Kang; Janey L Wiggs; Gail P Jarvik; Andrew N McDavid; Venkatraman E Seshan; Daniel B Mirel; Andrew Crenshaw; Nataliya Sharopova; Anastasia Wise; Jess Shen; David R Crosslin; David M Levine; Xiuwen Zheng; Jenna I Udren; Siiri Bennett; Sarah C Nelson; Stephanie M Gogarten; Matthew P Conomos; Patrick Heagerty; Teri Manolio; Louis R Pasquale; Christopher A Haiman; Neil Caporaso; Bruce S Weir
• Keywords: Uniparental disomy; SNP array; Chromothripsis; SNP; clone (Java method)

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).