Article | Published:

Detectable clonal mosaicism and its relationship to aging and cancer

Nature Genetics volume 44, pages 651658 (2012) | Download Citation

Abstract

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 × 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 × 10−11). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.

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Acknowledgements

This research was supported by the Intramural Research Program and by contract number HHSN261200800001E of the US National Institutes of Health (NIH), NCI. Support for each contributing study is listed in the Supplementary Note. We thank C. Laurie and B. Weir for constructive discussion and a comparison of methodology and results for the GENEVA study. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the National Cancer Institute, the National Institute for Occupational Safety and Health or the Maryland Cancer Registry.

Author information

Author notes

    • Luis A Pérez-Jurado
    •  & Stephen J Chanock

    These authors jointly directed this work.

Affiliations

  1. Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), Rockville, Maryland, USA.

    • Kevin B Jacobs
    • , Meredith Yeager
    • , Weiyin Zhou
    • , Sholom Wacholder
    • , Zhaoming Wang
    • , Amy Hutchinson
    • , Xiang Deng
    • , Chenwei Liu
    • , Marie-Josephe Horner
    • , Michael Cullen
    • , Caroline G Epstein
    • , Laurie Burdett
    • , Nilanjan Chatterjee
    • , Joshua Sampson
    • , Charles C Chung
    • , Joseph Kovaks
    • , Demetrius Albanes
    • , Stephanie J Weinstein
    • , Philip R Taylor
    • , Neal D Freedman
    • , Christian C Abnet
    • , Alisa M Goldstein
    • , Nan Hu
    • , Kai Yu
    • , Linda Liao
    • , Regina G Ziegler
    • , Jonine D Figueroa
    • , Montserrat Garcia-Closas
    • , Ludmila Prokunina-Olsson
    • , Dalsu Baris
    • , Maria Teresa Landi
    • , Lynn Goldin
    • , Melissa Rotunno
    • , Preetha Rajaraman
    • , Laura E Beane Freeman
    • , Patricia Hartge
    • , Peter D Inskip
    • , Annelie Landgren
    • , Debra T Silverman
    • , Julie B Mendelsohn
    • , Geoffrey S Tobias
    • , Laufey Amundadottir
    • , Rachael Z Stolzenberg-Solomon
    • , Sharon A Savage
    • , Lisa Mirabello
    • , Mark Purdue
    • , Wong-Ho Chow
    • , Lee E Moore
    • , Ann W Hsing
    • , Sonja I Berndt
    • , Amanda Black
    • , Nicolas Wentzensen
    • , Louise A Brinton
    • , Katherine A McGlynn
    • , Michael B Cook
    • , Barry I Graubard
    • , Christian P Kratz
    • , Mark H Greene
    • , Robert N Hoover
    • , Joseph F Fraumeni Jr
    • , Neil E Caporaso
    • , Margaret Tucker
    • , Nathaniel Rothman
    •  & Stephen J Chanock
  2. Core Genotyping Facility, SAIC-Frederick, Inc, NCI-Frederick, Frederick, Maryland, USA.

    • Kevin B Jacobs
    • , Meredith Yeager
    • , Weiyin Zhou
    • , Zhaoming Wang
    • , Amy Hutchinson
    • , Xiang Deng
    • , Chenwei Liu
    • , Michael Cullen
    •  & Laurie Burdett
  3. Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.

    • Benjamin Rodriguez-Santiago
    • , Olaya Villa
    • , Francisco X Real
    •  & Luis A Pérez-Jurado
  4. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain.

    • Benjamin Rodriguez-Santiago
    • , Olaya Villa
    •  & Luis A Pérez-Jurado
  5. Quantitative Genomic Medicine Laboratory, qGenomics, Barcelona, Spain.

    • Benjamin Rodriguez-Santiago
    •  & Olaya Villa
  6. Laboratory of Experimental Immunology, Center for Cancer Research, NCI-Frederick, Frederick, Maryland, USA.

    • Michael C Dean
  7. Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USA.

    • Susan M Gapstur
    • , Victoria L Stevens
    • , Lauren T Teras
    •  & Mia M Gaudet
  8. Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.

    • Jarmo Virtamo
  9. Department of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.

    • Jian-Min Yuan
  10. University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.

    • Jian-Min Yuan
  11. Shanxi Cancer Hospital, Taiyuan, People's Republic of China.

    • Ti Ding
    •  & Ze-Zhong Tang
  12. Department of Epidemiology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Beijing, People's Republic of China.

    • You-Lin Qiao
    •  & Jin-Hu Fan
  13. Shanghai Cancer Institute, Shanghai, People's Republic of China.

    • Yu-Tang Gao
    •  & Yong-Bing Xiang
  14. Saw Swee Hock School of Public Health, National University of Singapore, Singapore.

    • Woon-Puay Koh
  15. Department of Thoracic Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

    • Melinda C Aldrich
  16. Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

    • Melinda C Aldrich
    • , William J Blot
    • , Lisa B Signorello
    • , Xiao-Ou Shu
    •  & Wei Zheng
  17. Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

    • Christopher Amos
    •  & Xifeng Wu
  18. International Epidemiology Institute, Rockville, Maryland, USA.

    • William J Blot
    •  & Lisa B Signorello
  19. Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, USA.

    • Cathryn H Bock
    •  & Ann G Schwartz
  20. Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan, USA.

    • Cathryn H Bock
    •  & Ann G Schwartz
  21. Division of Cancer Control and Population Sciences, NCI, Bethesda, Maryland, USA.

    • Elizabeth M Gillanders
    •  & Krista A Zanetti
  22. Laboratory of Human Carcinogenesis, Center for Cancer Research, NCI, Bethesda, Maryland, USA.

    • Curtis C Harris
    •  & Krista A Zanetti
  23. Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, USA.

    • Christopher A Haiman
    • , Brian E Henderson
    • , Roberta McKean-Cowdin
    • , Fredrick Schumacher
    • , Daniel Stram
    •  & Donald A Barkauskas
  24. Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA.

    • Laurence N Kolonel
    •  & Loic Le Marchand
  25. Department of Health Disparities Research, Division of Office of the Vice-President, Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

    • Lorna H McNeill
  26. Center for Community-Engaged and Translational Research, Duncan Family Institute, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

    • Lorna H McNeill
  27. Department of Public Health Sciences, Henry Ford Hospital, Detroit, Michigan, USA.

    • Benjamin A Rybicki
  28. Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

    • Lisa B Signorello
    • , Xiao-Ou Shu
    •  & Wei Zheng
  29. Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, USA.

    • Margaret R Spitz
  30. Department of Neurological Surgery, University of California, San Francisco, California, USA.

    • John K Wiencke
    •  & Margaret Wrensch
  31. Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.

    • Montserrat Garcia-Closas
  32. Genetics and Molecular Epidemiology Group, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.

    • Nuria Malats
    •  & Gaelle Marenne
  33. Maine Cancer Registry, Augusta, Maine, USA.

    • Molly Schwenn
  34. Vermont Cancer Registry, Burlington, Vermont, USA.

    • Alison Johnson
  35. Department of Occupational and Environmental Health, University of Milan, Milan, Italy.

    • Dario Consonni
    •  & Pier Alberto Bertazzi
  36. Unit of Epidemiology, Fondazione Istituto di Ricevero e Cura a Carattere Scientifico (IRCCS), Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy.

    • Dario Consonni
    •  & Pier Alberto Bertazzi
  37. Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.

    • Ulrika Andersson
    • , Roger Henriksson
    •  & Beatrice S Melin
  38. Clinical and Translational Epidemiology Branch, Division of Cancer Control and Population Sciences, NCI, Bethesda, Maryland, USA.

    • Christine D Berg
    •  & Joanne W Elena
  39. Department of Ambulatory Care and Prevention, Harvard Medical School, Boston, Massachusetts, USA.

    • Julie E Buring
  40. Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

    • Julie E Buring
    • , J Michael Gaziano
    •  & Howard D Sesso
  41. National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Cincinnati, Ohio, USA.

    • Mary A Butler
    • , Tania Carreon
    •  & Avima M Ruder
  42. Division of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

    • Maria Feychting
    •  & Anders Ahlbom
  43. Division of Aging, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

    • J Michael Gaziano
  44. Massachusetts Veteran's Epidemiology, Research and Information Center, Geriatric Research Education and Clinical Center, Veterans Affairs Boston Healthcare System, Boston, Massachusetts, USA.

    • J Michael Gaziano
  45. Cancer Epidemiology Centre, The Cancer Council of Victoria, Melbourne, Victoria, Australia.

    • Graham G Giles
    •  & Gianluca Severi
  46. Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology, University of Melbourne, Melbourne, Victoria, Australia.

    • Graham G Giles
    •  & Gianluca Severi
  47. Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.

    • Goran Hallmans
  48. Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

    • Susan E Hankinson
    • , Brian M Wolpin
    • , Charles S Fuchs
    • , Edward L Giovannucci
    • , Peter Kraft
    •  & David J Hunter
  49. Department of Oncology, Karolinska University Hospital, Stockholm, Sweden.

    • Roger Henriksson
  50. Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark.

    • Christoffer Johansen
    •  & Anne Tjønneland
  51. Division of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.

    • Dominique S Michaud
    •  & Elio Riboli
  52. Department of Epidemiology, Division of Biology and Medicine, Brown University, Providence, Rhode Island, USA.

    • Dominique S Michaud
  53. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

    • Ulrike Peters
    • , Emily White
    • , Charles Kooperberg
    • , Andrea LaCroix
    •  & Margaret T Mandelson
  54. Department of Epidemiology, University of Washington, Seattle, Washington, USA.

    • Ulrike Peters
    •  & Emily White
  55. Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.

    • Kala Visvanathan
    •  & Judith A Hoffman Bolton
  56. Division of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

    • Alicja Wolk
  57. Department of Environmental Medicine, Division of Epidemiology, New York University School of Medicine, New York, New York, USA.

    • Anne Zeleniuch-Jacquotte
  58. National School of Public Health, Athens, Greece.

    • Manolis Kogevinas
  59. Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.

    • Manolis Kogevinas
    •  & Juan R Gonzalez
  60. Institut Municipal d'Investigació Mèdica (IMIM), Barcelona, Spain.

    • Manolis Kogevinas
    •  & Juan R Gonzalez
  61. Centro de Investigacion Biomedica en Red Epidemiologia y Salud Publica (CIBERESP), Barcelona, Spain.

    • Manolis Kogevinas
    •  & Juan R Gonzalez
  62. Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

    • Donghui Li
    •  & Manal Hassan
  63. Catalan Institute of Oncology (ICO), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain.

    • Eric J Duell
  64. Yale University School of Public Health, New Haven, Connecticut, USA.

    • Harvey A Risch
    •  & Herbert Yu
  65. Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.

    • Sara H Olson
  66. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

    • Brian M Wolpin
    •  & Charles S Fuchs
  67. Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.

    • Li Jiao
  68. Information Management Services, Silver Spring, Maryland, USA.

    • William Wheeler
  69. Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York, USA.

    • Alan A Arslan
  70. Department of Environmental Medicine, New York University School of Medicine, New York, New York, USA.

    • Alan A Arslan
  71. New York University Cancer Institute, New York, New York, USA.

    • Alan A Arslan
  72. Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands.

    • H Bas Bueno-de-Mesquita
  73. National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.

    • H Bas Bueno-de-Mesquita
  74. Fred A Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Toronto, Ontario, Canada.

    • Steven Gallinger
    • , Irene L Andrulis
    •  & Jay S Wunder
  75. Department of Laboratory Medicine and Pathology, School of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.

    • Myron D Gross
  76. Department of Epidemiology and Biostatistics, University of California, San Francisco, California, USA.

    • Elizabeth A Holly
    •  & Paige M Bracci
  77. Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

    • Alison P Klein
    •  & Michael Goggins
  78. Group Health Center for Health Studies, Seattle, Washington, USA.

    • Margaret T Mandelson
  79. Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.

    • Gloria Petersen
    •  & Kari G Rabe
  80. Institut National de la Santé et de la Recherche Médicale (INSERM), Paris-Sud University, Institut Gustave-Roussy, Villejuif, France.

    • Marie-Christine Boutron-Ruault
  81. Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

    • Federico Canzian
  82. Comprehensive Digestive Disease Center, University of California Irvine Medical Center, Orange, California, USA.

    • Kenneth Chang
  83. Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.

    • Michelle Cotterchio
  84. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.

    • Edward L Giovannucci
    • , Dimitrios Trichopoulos
    • , Peter Kraft
    •  & David J Hunter
  85. Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.

    • Edward L Giovannucci
  86. Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

    • Michael Goggins
  87. Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

    • Michael Goggins
  88. International Agency for Research on Cancer (IARC)/World Health Organization (WHO), Lyon, France.

    • Mazda Jenab
  89. Department of Public Health and Primary Care, Clinical Gerontology, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.

    • Kay-Tee Khaw
  90. Nutritional Epidemiology Unit, IRCCS, Istituto Nazionale dei Tumori, Milan, Italy.

    • Vittorio Krogh
  91. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.

    • Robert C Kurtz
  92. Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota, USA.

    • Robert R McWilliams
  93. Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece.

    • Dimitrios Trichopoulos
  94. Mount Sinai Hospital Christopher Sharp Centre for Surgery and Oncology, Toronto, Ontario, Canada.

    • Irene L Andrulis
    •  & Jay S Wunder
  95. Department of Pediatrics, Clínica Universidad de Navarra, Pamplona, Spain.

    • Ana Patiño García
    •  & Luis Sierrasesúmaga
  96. Department of Molecular Pharmacology, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York, USA.

    • Richard G Gorlick
  97. Department of Pediatrics, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York, USA.

    • Richard G Gorlick
  98. Department of Family Medicine and Public Health Sciences, Wayne State University, Detroit, Michigan, USA.

    • Kendra L Schwartz
  99. Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago, Chicago, Illinois, USA.

    • Faith G Davis
  100. Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.

    • Jolanta Lissowska
  101. Nofer Institute of Occupational Medicine, Lodz, Poland.

    • Beata Peplonska
  102. Zentrum für Kinderheilkunde und Jugendmedizin, Klinik für Pädiatrische Hämatologie und Onkologie, Medizinische Hochschule Hannover, Hannover, Germany.

    • Christian P Kratz
  103. Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.

    • Ralph L Erickson
  104. Synergie-Lyon-Cancer, Universite Lyon 1, Centre Leon Berard, Lyon, France.

    • Gilles Thomas
  105. Epithelial Carcinogenesis Group, CNIO, Madrid, Spain.

    • Francisco X Real

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Contributions

K.B.J., M.Y., W. Zhou, Z.W., X.D., C.L., S.W., N.E.C., M.T., N.R. and S.J.C. designed the study. K.B.J., M.Y., L.A.P.-J., W. Zhou, Z.W., S.W., N.E.C., N.R., M. Cullen, M.C.D., D.A., B.I.G., R.N.H., F.X.R. and S.J.C. interpreted the primary results. K.B.J., M.Y., L.A.P.-J., B.R.-S. and J.R.G. developed the study methods. K.B.J., M.Y., L.A.P.-J., W. Zhou, Z.W., X.D., C.L., M. Cullen, C.G.E., M.C.D., N.C., J.S. and C.C.C. analyzed the data. K.B.J., M.Y., W. Zhou, Z.W., X.D., C.L., A.H., L.B. and J.K. were responsible for production and analysis of the genotype data. K.B.J., M.Y. and S.W. performed statistical analysis. K.B.J., M.Y., S.W., M.-J.H. and S.J.C. drafted the manuscript. M.T., R.N.H., S.J.C. and J.F.F. provided vital programmatic and institutional support. J.R.G., N.E.C., M.T., N.R., S.J.C., S.M.G., V.L.S., L.T.T., M.M.G., D.A., S.J.W., J.V., P.R.T., N.D.F., C.C.A., A.M.G., N.H., K.Y., J.-M.Y., L.L., T.D., Y.-L.Q., Y.-T.G.,W.-P.K., Y.-B.X., Z.-Z.T., J.-H.F., M.C.A., C.A., W.J.B., C.H.B., E.M.G., C.C.H., C.A.H., B.E.H., L.N.K., L.L.M., L.H.M., B.A.R., A.G.S., L.B.S., M.R.S., J.K.W., M.W., X.W., K.A.Z., R.G.Z., J.D.F., M.G.-C., N.M., G.M., L.P.-O., D.B., M.S., A.J., M.T.L., L.G., D.C., P.A.B., M.R., P.R., U.A., L.E.B.F., C.D.B., J.E.B., M.A.B., T.C., M.F., A.A., J.M.G., G.G.G., G.H., S.E.H., P.H., R.H., P.D.I., C.J., A. Landgren, R.M.-C., D.S.M., B.S.M., U.P., A.M.R., H.D.S., G.S., X.-O.S., K.V., E.W., A.W., A.Z.-J., W. Zheng, D.T.S., M.K., O.V., D.L., E.J.D., H.A.R., S.H.O., C.K., B.M.W., L.J., M.H., W.W., A.A.A., H.B.B.-d.-M., C.S.F., S.G., M.D.G., E.A.H., A.P.K., A. LaCroix, M.T.M., G.P., M.-C.B.-R., P.M.B., F.C., K.C., M. Cotterchio, E.L.G., M.G., J.A.H.B., M.J., K.-T.K., V.K., R.C.K., R.R.M., J.B.M., K.G.R., E.R., A.T., G.S.T., D.T., J.W.E., H.Y., L.A., R.Z.S.-S., P.K., F.S., D.S., S.A.S., L.M., I.L.A., J.S.W., A.P.G., L.S., D.A.B., R.G.G., M.P., W.-H.C., L.E.M., K.L.S., F.G.D., A.W.H., S.I.B., A.B., N.W., L.A.B., J.L., B.P., K.A.M., M.B.C., B.I.G., C.P.K., M.H.G., R.L.E., D.J.H., G.T., R.N.H., F.X.R. and J.F.F. contributed data or samples. All authors contributed critical feedback, review and approval of the manuscript.

Competing interests

B.R.-S. and O.V. are currently employees of qGenomics, and L.A.P.-J. is a member of its scientific advisory board.

Corresponding author

Correspondence to Stephen J Chanock.

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Tables 1–3, Supplementary Figures 1–3 and Supplementary Note

Excel files

  1. 1.

    Supplementary Data

    Excel file containing an anonymized listing of coordinates for all detectable clonal mosaic events and their attributes

About this article

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DOI

https://doi.org/10.1038/ng.2270

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