UCL  IRIS
Institutional Research Information Service
UCL Logo
Please report any queries concerning the funding data grouped in the sections named "Externally Awarded" or "Internally Disbursed" (shown on the profile page) to your Research Finance Administrator. Your can find your Research Finance Administrator at https://www.ucl.ac.uk/finance/research/rs-contacts.php by entering your department
Please report any queries concerning the student data shown on the profile page to:

Email: portico-services@ucl.ac.uk

Help Desk: http://www.ucl.ac.uk/ras/portico/helpdesk
Publication Detail
The co-evolution of the genome and epigenome in colorectal cancer
  • Publication Type:
    Journal article
  • Authors:
    Heide T, Househam J, Cresswell GD, Spiteri I, Lynn C, Mossner M, Kimberley C, Fernandez-Mateos J, Chen B, Zapata L, James C, Barozzi I, Chkhaidze K, Nichol D, Gunasri V, Berner A, Schmidt M, Lakatos E, Baker A-M, Costa H, Mitchinson M, Piazza R, Jansen M, Caravagna G, Ramazzotti D, Shibata D, Bridgewater J, Rodriguez-Justo M, Magnani L, Graham TA, Sottoriva A
  • Publisher:
    Springer Science and Business Media LLC
  • Publication date:
    26/10/2022
  • Journal:
    Nature
  • Medium:
    Print-Electronic
  • Status:
    Accepted
  • Country:
    England
  • PII:
    10.1038/s41586-022-05202-1
  • Language:
    English
  • Keywords:
    Cancer genomics, Colorectal cancer, Computational biology and bioinformatics, Epigenomics, Tumour heterogeneity
  • Notes:
    © 2022 Springer Nature Limited. This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).
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 transformation4,5,6,7. 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.
Publication data is maintained in RPS. Visit https://rps.ucl.ac.uk
 More search options
UCL Researchers
Author
Research Department of Haematology
Author
Research Department of Pathology
Author
Research Department of Pathology
University College London - Gower Street - London - WC1E 6BT Tel:+44 (0)20 7679 2000

© UCL 1999–2011

Search by