Detectable clonal mosaicism from birth to old age and its relationship to cancer
Open accessAbstract
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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References 56 · Cited by 594
Research works printed but not linked: 1
- [2]Strachan T Read AP Human Molecular Genetics Wiley-Liss New York 1996
- Authors
- Laurie, C. C., Laurie, C. A., Rice, K., Doheny, K. F., Zelnick, L. R., McHugh, C. P., Ling, H., Hetrick, K. N., Pugh, E. W., Amos, C., Wei, Q., Wang, L.-E., Lee, J. E., Barnes, K. C., Hansel, N. N., Mathias, R., Daley, D., Beaty, T. H., Scott, A. F., Ruczinski, I., Scharpf, R. B., Bierut, L. J., Hartz, S. M., Landi, M. T., Freedman, N. D., Goldin, L. R., Ginsburg, D., Li, J., Desch, K. C., Strom, S. S., Blot, W. J., Signorello, L. B., Ingles, S. A., Chanock, S. J., Berndt, S. I., Le Marchand, L., Henderson, B. E., Monroe, K. R., Heit, J. A., de Andrade, M., Armasu, S. M., Regnier, C., Lowe, W. L., Hayes, M. G., Marazita, M. L., Feingold, E., Murray, J. C., Melbye, M., Feenstra, B., Kang, J. H., Wiggs, J. L., Jarvik, G. P., McDavid, A. N., Seshan, V. E., Mirel, D. B., Crenshaw, A., Sharopova, N., Wise, A., Shen, J., Crosslin, D. R., Levine, D. M., Zheng, X., Udren, J. I., Bennett, S., Nelson, S. C., Gogarten, S. M., Conomos, M. P., Heagerty, P., Manolio, T., Pasquale, L. R., Haiman, C. A., Caporaso, N., & Weir, B. S.
- Affiliations
- University of Washington (US)
- Johns Hopkins University (US)
- The University of Texas MD Anderson Cancer Center (US)
- University of British Columbia (CA)
- Washington University in St. Louis (US)
- National Institutes of Health (US)
- Howard Hughes Medical Institute (US)
- University of Michigan (US)
- Vanderbilt University (US)
- USC Norris Comprehensive Cancer Center (US)
- Mayo Clinic (US)
- Northwestern University (US)
- University of Pittsburgh (US)
- University of Iowa (US)
- Statens Serum Institut (DK)
- Brigham and Women's Hospital (US)
- Massachusetts Eye and Ear Infirmary (US)
- Fred Hutch Cancer Center (US)
- Memorial Sloan Kettering Cancer Center (US)
- Broad Institute (US)
- National Center for Biotechnology Information (US)
- Corresponding author
- Laurie, Cathy C
- ORCID
- Laurie, Cathy C
- Laurie, Cecelia A
- Rice, Kenneth
- Doheny, Kimberly F
- Zelnick, Leila R
- McHugh, Caitlin P
- Hetrick, Kurt N
- Wei, Qingyi
- Hansel, Nadia N
- Mathias, Rasika
- Daley, Denise
- Beaty, Terri H
- Scott, Alan F
- Ruczinski, Ingo
- Bierut, Laura J
- Hartz, Sarah M
- Landi, Maria Teresa
- Freedman, Neal D
- Goldin, Lynn R
- Ginsburg, David
- Li, Jun
- Desch, Karl C
- Blot, William J
- Ingles, Sue A
- Chanock, Stephen J
- Berndt, Sonja I
- Monroe, Kristine R
- Heit, John A
- Armasu, Sebastian M
- Lowe, William L
- Hayes, M Geoffrey
- Feingold, Eleanor
- Melbye, Mads
- Feenstra, Bjarke
- Wiggs, Janey L
- Jarvik, Gail P
- McDavid, Andrew N
- Seshan, Venkatraman E
- Crosslin, David R
- Levine, David M
- Zheng, Xiuwen
- Udren, Jenna I
- Nelson, Sarah C
- Gogarten, Stephanie M
- Conomos, Matthew P
- Manolio, Teri
- Pasquale, Louis R
- Caporaso, Neil
- Weir, Bruce S
- Venue
- Nature Genetics
- Published
- 2012-05-06
- Volume
- 44
- Issue
- 6
- Pages
- 642-650
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC3366033
- OpenAlex
- W2133920348
- Cited by
- 594
- References
- 56
- Citations by year
- 2026: 17 · 2025: 26 · 2024: 31 · 2023: 35 · 2022: 35 · 2021: 70 · 2020: 41 · 2019: 61 · 2018: 48 · 2017: 47 · 2016: 47 · 2015: 39 · 2014: 38 · 2013: 37 · 2012: 22
- FWCI
- 26.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (5u01hg004423-02, KL2TR000450)
- U.S. Public Health Service (HHSN268200782096C.)
- National Institute on Alcohol Abuse and Alcoholism (U10AA008401)
- National Heart, Lung, and Blood Institute (R01HL039693, R37HL039693)
- National Institute on Drug Abuse (K08DA032680, R01DA019963, R01DA013423)
- National Human Genome Research Institute (U01HG004735, U01-HG004423, U01HG004726, U01HG04424, U01HG004422, U01HG004738, U01HG004728, U01HG004415, U01HG004446, U01HG004424, U01HG004438, HHSN268200782096C)
- National Eye Institute (R01EY015473, R01EY015872, P30EY014104)
- National Cancer Institute (R29 CA70334, R01CA092447, CA63464, T32CA09168, U01CA063464, R37CA054281, R01CA054281, P01CA089392, R01CA063464, CA 54281, R29CA070334, CA1326792, R01CA100264, RC2CA148085, T32CA009168, Z01CP010200, P50CA093459)
- National Institute of General Medical Sciences (P01GM099568)
- National Institute of Dental and Craniofacial Research (U01DE018993, R01DE016148, U01DE018903, R01DE014899)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Keywords
- clonal mosaicism, peripheral blood, aging, uniparental disomy, chromosomal duplication, chromosomal deletion, cancer susceptibility, SNP array
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Aging, Child, Child, Preschool, Chromosome Aberrations, Chromosome Mapping, Female, Humans, Infant, Infant, Newborn, Male, Middle Aged, Mosaicism, Neoplasms, Genome-Wide Association Study, DNA Copy Number Variations
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