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


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).

SUBMITTER: Laurie CC 

PROVIDER: S-EPMC3366033 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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

Laurie Cathy C CC   Laurie Cecelia A CA   Rice Kenneth K   Doheny Kimberly F KF   Zelnick Leila R LR   McHugh Caitlin P CP   Ling Hua H   Hetrick Kurt N KN   Pugh Elizabeth W EW   Amos Chris C   Wei Qingyi Q   Wang Li-e LE   Lee Jeffrey E JE   Barnes Kathleen C KC   Hansel Nadia N NN   Mathias Rasika R   Daley Denise D   Beaty Terri H TH   Scott Alan F AF   Ruczinski Ingo I   Scharpf Rob B RB   Bierut Laura J LJ   Hartz Sarah M SM   Landi Maria Teresa MT   Freedman Neal D ND   Goldin Lynn R LR   Ginsburg David D   Li Jun J   Desch Karl C KC   Strom Sara S SS   Blot William J WJ   Signorello Lisa B LB   Ingles Sue A SA   Chanock Stephen J SJ   Berndt Sonja I SI   Le Marchand Loic L   Henderson Brian E BE   Monroe Kristine R KR   Heit John A JA   de Andrade Mariza M   Armasu Sebastian M SM   Regnier Cynthia C   Lowe William L WL   Hayes M Geoffrey MG   Marazita Mary L ML   Feingold Eleanor E   Murray Jeffrey C JC   Melbye Mads M   Feenstra Bjarke B   Kang Jae H JH   Wiggs Janey L JL   Jarvik Gail P GP   McDavid Andrew N AN   Seshan Venkatraman E VE   Mirel Daniel B DB   Crenshaw Andrew A   Sharopova Nataliya N   Wise Anastasia A   Shen Jess J   Crosslin David R DR   Levine David M DM   Zheng Xiuwen X   Udren Jenna I JI   Bennett Siiri S   Nelson Sarah C SC   Gogarten Stephanie M SM   Conomos Matthew P MP   Heagerty Patrick P   Manolio Teri T   Pasquale Louis R LR   Haiman Christopher A CA   Caporaso Neil N   Weir Bruce S BS  

Nature genetics 20120506 6


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  ...[more]

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