Detectable clonal mosaicism from birth to old age and its relationship to cancer Journal Article
| 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. |
| Article Title: | 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). © 2012 Nature America, Inc. All rights reserved. |
| Keywords: | adolescent; adult; child; aged; aged, 80 and over; child, preschool; middle aged; single nucleotide polymorphism; neoplasms; cancer susceptibility; multiple myeloma; genetic association; genome-wide association study; age; genome analysis; uniparental disomy; hematologic malignancy; myelodysplastic syndrome; nonhodgkin lymphoma; dna; clonal variation; infant; infant, newborn; microarray analysis; aging; chromosome aberrations; chromosome deletion; chronic lymphatic leukemia; karyotype; dna determination; birth; chromosome mapping; dna copy number variations; myeloid leukemia; mosaicism; chromosome duplication; clonal mosaicism |
| Journal Title: | Nature Genetics |
| Volume: | 44 |
| Issue: | 6 |
| ISSN: | 1061-4036 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2012-05-06 |
| Start Page: | 642 |
| End Page: | 650 |
| Language: | English |
| DOI: | 10.1038/ng.2271 |
| PROVIDER: | scopus |
| PMCID: | PMC3366033 |
| PUBMED: | 22561516 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 2" - "Export Date: 2 July 2012" - "CODEN: NGENE" - "Source: Scopus" |
