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

• Published in: Nature genetics Vol. 44; no. 6; pp. 642 - 650
• Main Authors: Laurie, Cathy C, Laurie, Cecelia A, Rice, Kenneth, Doheny, Kimberly F, Zelnick, Leila R, McHugh, Caitlin P, Ling, Hua, Hetrick, Kurt N, Pugh, Elizabeth W, Amos, Chris, Wei, Qingyi, Wang, Li-e, Lee, Jeffrey E, Barnes, Kathleen C, Hansel, Nadia N, Mathias, Rasika, Daley, Denise, Beaty, Terri H, Scott, Alan F, Ruczinski, Ingo, Scharpf, Rob B, Bierut, Laura J, Hartz, Sarah M, Landi, Maria Teresa, Freedman, Neal D, Goldin, Lynn R, Ginsburg, David, Li, Jun, Desch, Karl C, Strom, Sara S, Blot, William J, Signorello, Lisa B, Ingles, Sue A, Chanock, Stephen J, Berndt, Sonja I, Le Marchand, Loic, Henderson, Brian E, Monroe, Kristine R, Heit, John A, de Andrade, Mariza, Armasu, Sebastian M, Regnier, Cynthia, Lowe, William L, Hayes, M Geoffrey, Marazita, Mary L, Feingold, Eleanor, Murray, Jeffrey C, Melbye, Mads, Feenstra, Bjarke, Kang, Jae H, Wiggs, Janey L, Jarvik, Gail P, McDavid, Andrew N, Seshan, Venkatraman E, Mirel, Daniel B, Crenshaw, Andrew, Sharopova, Nataliya, Wise, Anastasia, Shen, Jess, Crosslin, David R, Levine, David M, Zheng, Xiuwen, Udren, Jenna I, Bennett, Siiri, Nelson, Sarah C, Gogarten, Stephanie M, Conomos, Matthew P, Heagerty, Patrick, Manolio, Teri, Pasquale, Louis R, Haiman, Christopher A, Caporaso, Neil, Weir, Bruce S
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.06.2012; Nature Publishing Group
• Subjects: 631/208/205/2138; 631/208/2489/1381/1661; 631/208/68; Adolescent; Adult; Aged; Aged, 80 and over; Aging - genetics; Agriculture; Animal Genetics and Genomics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Child; Child, Preschool; Chromosome Aberrations; Chromosome Mapping; Chromosomes; DNA Copy Number Variations; DNA microarrays; Female; Fundamental and applied biological sciences. Psychology; Gene Function; Genetic testing; Genetics of eukaryotes. Biological and molecular evolution; Genome-Wide Association Study; Genomes; Hematology; Human Genetics; Humans; Infant; Infant, Newborn; Karyotypes; Lung cancer; Male; Methods; Middle Aged; Molecular and cellular biology; Mosaicism; Neoplasms - genetics; Single nucleotide polymorphisms; Studies; United States; Mosaicism; Malignant tumor; Birth; Age; Cancer
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.2271

Cathy Laurie and colleagues detect mosaicism for large chromosomal abnormalities in peripheral blood in a subset of healthy individuals. They show that the frequency of such events increases with age and is associated with elevated risk of developing a subsequent hematological cancer. 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).