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

TitleDetectable clonal mosaicism from birth to old age and its relationship to cancer.
Publication TypeJournal Article
Year of Publication2012
AuthorsLaurie, CC, Laurie, CA, Rice, K, Doheny, KF, Zelnick, LR, McHugh, CP, Ling, H, Hetrick, KN, Pugh, EW, Amos, C, Wei, Q, Wang, L-e, Lee, JE, Barnes, KC, Hansel, NN, Mathias, R, Daley, D, Beaty, TH, Scott, AF, Ruczinski, I, Scharpf, RB, Bierut, LJ, Hartz, SM, Landi, MTeresa, Freedman, ND, Goldin, LR, Ginsburg, D, Li, J, Desch, KC, Strom, SS, Blot, WJ, Signorello, LB, Ingles, SA, Chanock, SJ, Berndt, SI, Le Marchand, L, Henderson, BE, Monroe, KR, Heit, JA, de Andrade, M, Armasu, SM, Regnier, C, Lowe, WL, M Hayes, G, Marazita, ML, Feingold, E, Murray, JC, Melbye, M, Feenstra, B, Kang, JH, Wiggs, JL, Jarvik, GP, McDavid, AN, Seshan, VE, Mirel, DB, Crenshaw, A, Sharopova, N, Wise, A, Shen, J, Crosslin, DR, Levine, DM, Zheng, X, Udren, JI, Bennett, S, Nelson, SC, Gogarten, SM, Conomos, MP, Heagerty, P, Manolio, T, Pasquale, LR, Haiman, CA, Caporaso, N, Weir, BS
JournalNat Genet
Volume44
Issue6
Pagination642-50
Date Published2012 Jun
ISSN1546-1718
KeywordsAdolescent, Adult, Aged, Aged, 80 and over, Aging, Child, Child, Preschool, Chromosome Aberrations, Chromosome Mapping, DNA Copy Number Variations, Female, Genome-Wide Association Study, Humans, Infant, Infant, Newborn, Male, Middle Aged, Mosaicism, Neoplasms
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).

DOI10.1038/ng.2271
Alternate JournalNat. Genet.
PubMed ID22561516
PubMed Central IDPMC3366033
Grant ListCA1326792 / CA / NCI NIH HHS / United States
CA54281 / CA / NCI NIH HHS / United States
CA63464 / CA / NCI NIH HHS / United States
HHSN268200-782096C / / PHS HHS / United States
HHSN268200782096C / / PHS HHS / United States
K08 DA032680 / DA / NIDA NIH HHS / United States
KL2 TR000450 / TR / NCATS NIH HHS / United States
P01CA089392 / CA / NCI NIH HHS / United States
P50 CA093459 / CA / NCI NIH HHS / United States
P50CA093459 / CA / NCI NIH HHS / United States
R01 EY015473 / EY / NEI NIH HHS / United States
R01CA100264 / CA / NCI NIH HHS / United States
R01DA013423 / DA / NIDA NIH HHS / United States
R01DA019963 / DA / NIDA NIH HHS / United States
R01DE014899 / DE / NIDCR NIH HHS / United States
R01EY015473 / EY / NEI NIH HHS / United States
R01EY015872 / EY / NEI NIH HHS / United States
R29CA70334 / CA / NCI NIH HHS / United States
R37 HL 039693 / HL / NHLBI NIH HHS / United States
RC2 CA148085 / CA / NCI NIH HHS / United States
T32 CA09168 / CA / NCI NIH HHS / United States
U01 HG004446 / HG / NHGRI NIH HHS / United States
U01 HG004446 / HG / NHGRI NIH HHS / United States
U01 HG004446-01 / HG / NHGRI NIH HHS / United States
U01 HG004446-02 / HG / NHGRI NIH HHS / United States
U01 HG004446-03 / HG / NHGRI NIH HHS / United States
U01 HG004446-03S1 / HG / NHGRI NIH HHS / United States
U01 HG004446-03S2 / HG / NHGRI NIH HHS / United States
U01 HG004446-04 / HG / NHGRI NIH HHS / United States
U01 HG004446-04S1 / HG / NHGRI NIH HHS / United States
U01DE018903 / DE / NIDCR NIH HHS / United States
U01DE018993 / DE / NIDCR NIH HHS / United States
U01HG004415 / HG / NHGRI NIH HHS / United States
U01HG004422 / HG / NHGRI NIH HHS / United States
U01HG004423 / HG / NHGRI NIH HHS / United States
U01HG004438 / HG / NHGRI NIH HHS / United States
U01HG004726 / HG / NHGRI NIH HHS / United States
U01HG004728 / HG / NHGRI NIH HHS / United States
U01HG004735 / HG / NHGRI NIH HHS / United States
U01HG004738 / HG / NHGRI NIH HHS / United States
U01HG04424 / HG / NHGRI NIH HHS / United States
U10AA008401 / AA / NIAAA NIH HHS / United States
/ / Howard Hughes Medical Institute / United States