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

Cathy C. Laurie*, Cecelia A. Laurie, Kenneth Rice, Kimberly F. Doheny, Leila R. Zelnick, Caitlin P. McHugh, Hua Ling, Kurt N. Hetrick, Elizabeth W. Pugh, Chris Amos, Qingyi Wei, Li E. Wang, Jeffrey E. Lee, Kathleen C. Barnes, Nadia N. Hansel, Rasika Mathias, Denise Daley, Terri H. Beaty, Alan F. Scott, Ingo RuczinskiRob B. Scharpf, Laura J. Bierut, Sarah M. Hartz, Maria Teresa Landi, Neal D. Freedman, Lynn R. Goldin, David Ginsburg, Jun Li, Karl C. Desch, Sara S. Strom, William J. Blot, Lisa B. Signorello, Sue A. Ingles, Stephen J. Chanock, Sonja I. Berndt, Loic Le Marchand, Brian E. Henderson, Kristine R. Monroe, John A. Heit, Mariza De Andrade, Sebastian M. Armasu, Cynthia Regnier, William L. Lowe, M. Geoffrey Hayes, Mary L. Marazita, Eleanor Feingold, Jeffrey C. Murray, Mads Melbye, Bjarke Feenstra, Jae H. Kang, Janey L. Wiggs, Gail P. Jarvik, Andrew N. McDavid, Venkatraman E. Seshan, Daniel B. Mirel, Andrew Crenshaw, Nataliya Sharopova, Anastasia Wise, Jess Shen, David R. Crosslin, David M. Levine, Xiuwen Zheng, Jenna I. Udren, Siiri Bennett, Sarah C. Nelson, Stephanie M. Gogarten, Matthew P. Conomos, Patrick Heagerty, Teri Manolio, Louis R. Pasquale, Christopher A. Haiman, Neil Caporaso, Bruce S. Weir

*Corresponding author for this work

Research output: Contribution to journalArticle

286 Citations (Scopus)

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).

Original languageEnglish (US)
Pages (from-to)642-650
Number of pages9
JournalNature Genetics
Volume44
Issue number6
DOIs
StatePublished - Jun 1 2012

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Mosaicism
Parturition
Neoplasms
Chromosome Duplication
Uniparental Disomy
Abnormal Karyotype
Genome-Wide Association Study
Single Nucleotide Polymorphism
Confidence Intervals
DNA
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Laurie, C. C., Laurie, C. A., Rice, K., Doheny, K. F., Zelnick, L. R., McHugh, C. P., ... Weir, B. S. (2012). Detectable clonal mosaicism from birth to old age and its relationship to cancer. Nature Genetics, 44(6), 642-650. https://doi.org/10.1038/ng.2271
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. / Detectable clonal mosaicism from birth to old age and its relationship to cancer. In: Nature Genetics. 2012 ; Vol. 44, No. 6. pp. 642-650.
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Laurie, CC, Laurie, CA, Rice, K, Doheny, KF, Zelnick, LR, McHugh, CP, Ling, H, Hetrick, KN, Pugh, EW, Amos, C, Wei, Q, Wang, LE, Lee, JE, Barnes, KC, Hansel, NN, Mathias, R, Daley, D, Beaty, TH, Scott, AF, Ruczinski, I, Scharpf, RB, Bierut, LJ, Hartz, SM, Landi, MT, 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, Hayes, MG, 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 2012, 'Detectable clonal mosaicism from birth to old age and its relationship to cancer', Nature Genetics, vol. 44, no. 6, pp. 642-650. https://doi.org/10.1038/ng.2271

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

In: Nature Genetics, Vol. 44, No. 6, 01.06.2012, p. 642-650.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Detectable clonal mosaicism from birth to old age and its relationship to cancer

AU - Laurie, Cathy C.

AU - Laurie, Cecelia A.

AU - Rice, Kenneth

AU - Doheny, Kimberly F.

AU - Zelnick, Leila R.

AU - McHugh, Caitlin P.

AU - Ling, Hua

AU - Hetrick, Kurt N.

AU - Pugh, Elizabeth W.

AU - Amos, Chris

AU - Wei, Qingyi

AU - Wang, Li E.

AU - Lee, Jeffrey E.

AU - Barnes, Kathleen C.

AU - Hansel, Nadia N.

AU - Mathias, Rasika

AU - Daley, Denise

AU - Beaty, Terri H.

AU - Scott, Alan F.

AU - Ruczinski, Ingo

AU - Scharpf, Rob B.

AU - Bierut, Laura J.

AU - Hartz, Sarah M.

AU - Landi, Maria Teresa

AU - Freedman, Neal D.

AU - Goldin, Lynn R.

AU - Ginsburg, David

AU - Li, Jun

AU - Desch, Karl C.

AU - Strom, Sara S.

AU - Blot, William J.

AU - Signorello, Lisa B.

AU - Ingles, Sue A.

AU - Chanock, Stephen J.

AU - Berndt, Sonja I.

AU - Le Marchand, Loic

AU - Henderson, Brian E.

AU - Monroe, Kristine R.

AU - Heit, John A.

AU - De Andrade, Mariza

AU - Armasu, Sebastian M.

AU - Regnier, Cynthia

AU - Lowe, William L.

AU - Hayes, M. Geoffrey

AU - Marazita, Mary L.

AU - Feingold, Eleanor

AU - Murray, Jeffrey C.

AU - Melbye, Mads

AU - Feenstra, Bjarke

AU - Kang, Jae H.

AU - Wiggs, Janey L.

AU - Jarvik, Gail P.

AU - McDavid, Andrew N.

AU - Seshan, Venkatraman E.

AU - Mirel, Daniel B.

AU - Crenshaw, Andrew

AU - Sharopova, Nataliya

AU - Wise, Anastasia

AU - Shen, Jess

AU - Crosslin, David R.

AU - Levine, David M.

AU - Zheng, Xiuwen

AU - Udren, Jenna I.

AU - Bennett, Siiri

AU - Nelson, Sarah C.

AU - Gogarten, Stephanie M.

AU - Conomos, Matthew P.

AU - Heagerty, Patrick

AU - Manolio, Teri

AU - Pasquale, Louis R.

AU - Haiman, Christopher A.

AU - Caporaso, Neil

AU - Weir, Bruce S.

PY - 2012/6/1

Y1 - 2012/6/1

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AB - 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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Laurie CC, Laurie CA, Rice K, Doheny KF, Zelnick LR, McHugh CP et al. Detectable clonal mosaicism from birth to old age and its relationship to cancer. Nature Genetics. 2012 Jun 1;44(6):642-650. https://doi.org/10.1038/ng.2271