Detectable clonal mosaicism and its relationship to aging and cancer

被引：450

作者：

Jacobs, Kevin B. ^{[1
,2
]}

Yeager, Meredith ^{[1
,2
]}

Zhou, Weiyin ^{[1
,2
]}

Wacholder, Sholom ^{[1
]}

Wang, Zhaoming ^{[1
,2
]}

Rodriguez-Santiago, Benjamin ^{[3
,4
,5
]}

Hutchinson, Amy ^{[1
,2
]}

Deng, Xiang ^{[1
,2
]}

Liu, Chenwei ^{[1
,2
]}

Horner, Marie-Josephe ^{[1
]}

Cullen, Michael ^{[1
,2
]}

Epstein, Caroline G. ^{[1
]}

Burdett, Laurie ^{[1
,2
]}

Dean, Michael C. ^{[6
]}

Chatterjee, Nilanjan ^{[1
]}

Sampson, Joshua ^{[1
]}

Chung, Charles C. ^{[1
]}

Kovaks, Joseph ^{[1
]}

Gapstur, Susan M. ^{[7
]}

Stevens, Victoria L. ^{[7
]}

Teras, Lauren T. ^{[7
]}

Gaudet, Mia M. ^{[7
]}

Albanes, Demetrius ^{[1
]}

Weinstein, Stephanie J. ^{[1
]}

Virtamo, Jarmo ^{[8
]}

Taylor, Philip R. ^{[1
]}

Freedman, Neal D. ^{[1
]}

Abnet, Christian C. ^{[1
]}

Goldstein, Alisa M. ^{[1
]}

Hu, Nan ^{[1
]}

Yu, Kai ^{[1
]}

Yuan, Jian-Min ^{[9
,10
]}

Liao, Linda ^{[1
]}

Ding, Ti ^{[11
]}

Qiao, You-Lin ^{[12
]}

Gao, Yu-Tang ^{[13
]}

Koh, Woon-Puay ^{[14
]}

Xiang, Yong-Bing ^{[13
]}

Tang, Ze-Zhong ^{[11
]}

Fan, Jin-Hu ^{[12
]}

Aldrich, Melinda C. ^{[15
,16
]}

Amos, Christopher ^{[17
]}

Blot, William J. ^{[16
,18
]}

Bock, Cathryn H. ^{[19
,20
]}

Gillanders, Elizabeth M. ^{[21
]}

Harris, Curtis C. ^{[22
]}

Haiman, Christopher A. ^{[23
]}

Henderson, Brian E. ^{[23
]}

Kolonel, Laurence N. ^{[24
]}

Le Marchand, Loic ^{[24
]}

机构：

[1] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA

[2] NCI, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD 21701 USA

[3] Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona, Spain

[4] Ctr Invest Biomed Red Enfermedades Raras CIBERER, Barcelona, Spain

[5] qGenomics, Quantitat Genom Med Lab, Barcelona, Spain

[6] NCI, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21701 USA

[7] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA

[8] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland

[9] Univ Minnesota, Sch Publ Hlth, Dept Epidemiol & Community Hlth, Minneapolis, MN USA

[10] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA

[11] Shanxi Canc Hosp, Taiyuan, Peoples R China

[12] Chinese Acad Med Sci, Dept Epidemiol, Canc Inst Hosp, Beijing 100730, Peoples R China

[13] Shanghai Canc Inst, Shanghai, Peoples R China

[14] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore

[15] Vanderbilt Univ, Sch Med, Dept Thorac Surg, Nashville, TN 37212 USA

[16] Vanderbilt Univ, Med Ctr, Dept Med, Div Epidemiol,Vanderbilt Epidemiol Ctr, Nashville, TN USA

[17] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Div Canc Prevent & Populat Sci, Houston, TX 77030 USA

[18] Int Epidemiol Inst, Rockville, MD USA

[19] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA

[20] Wayne State Univ, Sch Med, Dept Oncol, Detroit, MI USA

[21] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA

[22] NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA

[23] Univ So Calif, Keck Sch Med, Dept Prevent Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA

[24] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA

[25] Univ Texas MD Anderson Canc Ctr, Dept Hlth Dispar Res, Div Off Vice President Canc Prevent & Populat Sci, Houston, TX 77030 USA

[26] Univ Texas MD Anderson Canc Ctr, Ctr Community Engaged & Translat Res, Duncan Family Inst, Houston, TX 77030 USA

[27] Henry Ford Hosp, Dept Publ Hlth Sci, Detroit, MI 48202 USA

[28] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 USA

[29] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA

[30] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA

[31] Inst Canc Res, Div Genet & Epidemiol, London SW3 6JB, England

[32] CNIO, Genet & Mol Epidemiol Grp, Madrid, Spain

[33] Maine Canc Registry, Augusta, ME USA

[34] Vermont Canc Registry, Burlington, VT USA

[35] Univ Milan, Dept Occupat & Environm Hlth, Milan, Italy

[36] Osped Maggiore Policlin Mangiagalli & Regina Elen, Unit Epidemiol, Fdn Ist Ricevero & Cura Carattere Sci IRCCS, Milan, Italy

[37] Umea Univ, Dept Radiat Sci, Umea, Sweden

[38] NCI, Clin & Translat Epidemiol Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA

[39] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA

[40] Harvard Univ, Brigham & Womens Hosp, Div Prevent Med, Sch Med, Boston, MA 02115 USA

[41] NIOSH, Ctr Dis Control & Prevent, Cincinnati, OH 45226 USA

[42] Karolinska Inst, Inst Environm Med, Div Epidemiol, S-10401 Stockholm, Sweden

[43] Harvard Univ, Sch Med, Div Aging, Brigham & Womens Hosp, Boston, MA 02115 USA

[44] Vet Affairs Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA

[45] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia

[46] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia

[47] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden

[48] Harvard Univ, Sch Med, Channing Lab, Dept Med,Brigham & Womens Hosp, Boston, MA 02115 USA

[49] Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden

[50] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark

来源：

NATURE GENETICS | 2012年 / 44卷 / 06期

基金：

美国国家卫生研究院;

关键词：

CHRONIC LYMPHOCYTIC-LEUKEMIA; GENOMIC IMBALANCES; MAFFUCCI SYNDROME; OLLIER DISEASE; MUTATIONS; SUSCEPTIBILITY; ASSOCIATION; ABERRATIONS; MECHANISMS; ANEUPLOIDY;

D O I：

10.1038/ng.2270

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of > 2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 x 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 x 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.

引用

页码：651 / U68

页数：10

共 43 条

[1] Approximate is better than "exact" for interval estimation of binomial proportions [J].

Agresti, A ;

Coull, BA .

AMERICAN STATISTICIAN, 1998, 52 (02) :119-126

[2] NEW LOOK AT STATISTICAL-MODEL IDENTIFICATION [J].

AKAIKE, H .

IEEE TRANSACTIONS ON AUTOMATIC CONTROL, 1974, AC19 (06) :716-723

[3] Ollier disease and Maffucci syndrome are caused by somatic mosaic mutations of IDH1 and IDH2 [J].

Amary, M. Fernanda ;

Damato, Stephen ;

Halai, Dina ;

Eskandarpour, Malihe ;

Berisha, Fitim ;

Bonar, Fiona ;

McCarthy, Stan ;

Fantin, Valeria R. ;

Straley, Kimberly S. ;

Lobo, Samira ;

Aston, Will ;

Green, Claire L. ;

Gale, Rosemary E. ;

Tirabosco, Roberto ;

Futreal, Andrew ;

Campbell, Peter ;

Presneau, Nadege ;

Flanagan, Adrienne M. .

NATURE GENETICS, 2011, 43 (12) :1262-U129

[4] MEG3 imprinted gene contribution in tumorigenesis [J].

Benetatos, Leonidas ;

Vartholomatos, George ;

Hatzimichael, Eleftheria .

INTERNATIONAL JOURNAL OF CANCER, 2011, 129 (04) :773-779

[5] Comprehensive genomic characterization defines human glioblastoma genes and core pathways [J].

Chin, L. ;

Meyerson, M. ;

Aldape, K. ;

Bigner, D. ;

Mikkelsen, T. ;

VandenBerg, S. ;

Kahn, A. ;

Penny, R. ;

Ferguson, M. L. ;

Gerhard, D. S. ;

Getz, G. ;

Brennan, C. ;

Taylor, B. S. ;

Winckler, W. ;

Park, P. ;

Ladanyi, M. ;

Hoadley, K. A. ;

Verhaak, R. G. W. ;

Hayes, D. N. ;

Spellman, Paul T. ;

Absher, D. ;

Weir, B. A. ;

Ding, L. ;

Wheeler, D. ;

Lawrence, M. S. ;

Cibulskis, K. ;

Mardis, E. ;

Zhang, Jinghui ;

Wilson, R. K. ;

Donehower, L. ;

Wheeler, D. A. ;

Purdom, E. ;

Wallis, J. ;

Laird, P. W. ;

Herman, J. G. ;

Schuebel, K. E. ;

Weisenberger, D. J. ;

Baylin, S. B. ;

Schultz, N. ;

Yao, Jun ;

Wiedemeyer, R. ;

Weinstein, J. ;

Sander, C. ;

Gibbs, R. A. ;

Gray, J. ;

Kucherlapati, R. ;

Lander, E. S. ;

Myers, R. M. ;

Perou, C. M. ;

McLendon, Roger .

NATURE, 2008, 455 (7216) :1061-1068

[6] Mechanisms of mosaicism, chimerism and uniparental disomy identified by single nucleotide polymorphism array analysis [J].

Conlin, Laura K. ;

Thiel, Brian D. ;

Bonnemann, Carsten G. ;

Medne, Livija ;

Ernst, Linda M. ;

Zackai, Elaine H. ;

Deardorff, Matthew A. ;

Krantz, Ian D. ;

Hakonarson, Hakon ;

Spinner, Nancy B. .

HUMAN MOLECULAR GENETICS, 2010, 19 (07) :1263-1275

[7] Comparative analyses of seven algorithms for copy number variant identification from single nucleotide polymorphism arrays [J].

Dellinger, Andrew E. ;

Saw, Seang-Mei ;

Goh, Liang K. ;

Seielstad, Mark ;

Young, Terri L. ;

Li, Yi-Ju .

NUCLEIC ACIDS RESEARCH, 2010, 38 (09) :e105

[8] Adjustment of genomic waves in signal intensities from whole-genome SNP genotyping platforms [J].

Diskin, Sharon J. ;

Li, Mingyao ;

Hou, Cuiping ;

Yang, Shuzhang ;

Glessner, Joseph ;

Hakonarson, Hakon ;

Bucan, Maja ;

Maris, John M. ;

Wang, Kai .

NUCLEIC ACIDS RESEARCH, 2008, 36 (19)

[9] Genomic aberrations and survival in chronic lymphocytic leukemia. [J].

Döhner, H ;

Stilgenbauer, S ;

Benner, A ;

Leupolt, E ;

Kröber, A ;

Bullinger, L ;

Döhner, K ;

Bentz, M ;

Lichter, P .

NEW ENGLAND JOURNAL OF MEDICINE, 2000, 343 (26) :1910-1916

[10] COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer [J].

Forbes, Simon A. ;

Bindal, Nidhi ;

Bamford, Sally ;

Cole, Charlotte ;

Kok, Chai Yin ;

Beare, David ;

Jia, Mingming ;

Shepherd, Rebecca ;

Leung, Kenric ;

Menzies, Andrew ;

Teague, Jon W. ;

Campbell, Peter J. ;

Stratton, Michael R. ;

Futreal, P. Andrew .

NUCLEIC ACIDS RESEARCH, 2011, 39 :D945-D950

← 1 2 3 4 5 →