IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v611y2022i7937d10.1038_s41586-022-05202-1.html
   My bibliography  Save this article

The co-evolution of the genome and epigenome in colorectal cancer

Author

Listed:
  • Timon Heide

    (The Institute of Cancer Research
    Human Technopole)

  • Jacob Househam

    (The Institute of Cancer Research
    Queen Mary University of London)

  • George D. Cresswell

    (The Institute of Cancer Research)

  • Inmaculada Spiteri

    (The Institute of Cancer Research)

  • Claire Lynn

    (The Institute of Cancer Research)

  • Maximilian Mossner

    (The Institute of Cancer Research
    Queen Mary University of London)

  • Chris Kimberley

    (Queen Mary University of London)

  • Javier Fernandez-Mateos

    (The Institute of Cancer Research)

  • Bingjie Chen

    (The Institute of Cancer Research)

  • Luis Zapata

    (The Institute of Cancer Research)

  • Chela James

    (The Institute of Cancer Research)

  • Iros Barozzi

    (Imperial College London
    Medical University of Vienna)

  • Ketevan Chkhaidze

    (The Institute of Cancer Research)

  • Daniel Nichol

    (The Institute of Cancer Research)

  • Vinaya Gunasri

    (The Institute of Cancer Research
    Queen Mary University of London)

  • Alison Berner

    (Queen Mary University of London)

  • Melissa Schmidt

    (Queen Mary University of London)

  • Eszter Lakatos

    (The Institute of Cancer Research
    Queen Mary University of London)

  • Ann-Marie Baker

    (The Institute of Cancer Research
    Queen Mary University of London)

  • Helena Costa

    (University College London)

  • Miriam Mitchinson

    (University College London)

  • Rocco Piazza

    (University of Milano-Bicocca)

  • Marnix Jansen

    (University College London)

  • Giulio Caravagna

    (The Institute of Cancer Research
    University of Triest)

  • Daniele Ramazzotti

    (University of Milano-Bicocca)

  • Darryl Shibata

    (University of Southern California Keck School of Medicine)

  • John Bridgewater

    (University College London)

  • Manuel Rodriguez-Justo

    (University College London)

  • Luca Magnani

    (Imperial College London)

  • Trevor A. Graham

    (The Institute of Cancer Research
    Queen Mary University of London)

  • Andrea Sottoriva

    (The Institute of Cancer Research
    Human Technopole)

Abstract

Colorectal malignancies are a leading cause of cancer-related death1 and have undergone extensive genomic study2,3. However, DNA mutations alone do not fully explain malignant transformation4–7. Here we investigate the co-evolution of the genome and epigenome of colorectal tumours at single-clone resolution using spatial multi-omic profiling of individual glands. We collected 1,370 samples from 30 primary cancers and 8 concomitant adenomas and generated 1,207 chromatin accessibility profiles, 527 whole genomes and 297 whole transcriptomes. We found positive selection for DNA mutations in chromatin modifier genes and recurrent somatic chromatin accessibility alterations, including in regulatory regions of cancer driver genes that were otherwise devoid of genetic mutations. Genome-wide alterations in accessibility for transcription factor binding involved CTCF, downregulation of interferon and increased accessibility for SOX and HOX transcription factor families, suggesting the involvement of developmental genes during tumourigenesis. Somatic chromatin accessibility alterations were heritable and distinguished adenomas from cancers. Mutational signature analysis showed that the epigenome in turn influences the accumulation of DNA mutations. This study provides a map of genetic and epigenetic tumour heterogeneity, with fundamental implications for understanding colorectal cancer biology.

Suggested Citation

  • Timon Heide & Jacob Househam & George D. Cresswell & Inmaculada Spiteri & Claire Lynn & Maximilian Mossner & Chris Kimberley & Javier Fernandez-Mateos & Bingjie Chen & Luis Zapata & Chela James & Iros, 2022. "The co-evolution of the genome and epigenome in colorectal cancer," Nature, Nature, vol. 611(7937), pages 733-743, November.
    • Handle: RePEc:nat:nature:v:611:y:2022:i:7937:d:10.1038_s41586-022-05202-1
    DOI: 10.1038/s41586-022-05202-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-022-05202-1
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/s41586-022-05202-1?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Bingjie Chen & Daniele Ramazzotti & Timon Heide & Inmaculada Spiteri & Javier Fernandez-Mateos & Chela James & Luca Magnani & Trevor A. Graham & Andrea Sottoriva, 2023. "Contribution of pks+ E. coli mutations to colorectal carcinogenesis," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    2. Giulia Schiroli & Vinay Kartha & Fabiana M. Duarte & Trine A. Kristiansen & Christina Mayerhofer & Rojesh Shrestha & Andrew Earl & Yan Hu & Tristan Tay & Catherine Rhee & Jason D. Buenrostro & David T, 2024. "Cell of origin epigenetic priming determines susceptibility to Tet2 mutation," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:611:y:2022:i:7937:d:10.1038_s41586-022-05202-1. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.