IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms12072.html
   My bibliography  Save this article

Patients with genetically heterogeneous synchronous colorectal cancer carry rare damaging germline mutations in immune-related genes

Author

Listed:
  • Matteo Cereda

    (King’s College London)

  • Gennaro Gambardella

    (King’s College London)

  • Lorena Benedetti

    (King’s College London)

  • Fabio Iannelli

    (IFOM, FIRC Institute of Molecular Oncology)

  • Dominic Patel

    (Cancer Institute, University College London)

  • Gianluca Basso

    (Laboratory of Molecular Gastroenterology, Humanitas Research Hospital)

  • Rosalinda F. Guerra

    (King’s College London)

  • Thanos P. Mourikis

    (King’s College London)

  • Ignazio Puccio

    (Cancer Institute, University College London)

  • Shruti Sinha

    (King’s College London)

  • Luigi Laghi

    (Laboratory of Molecular Gastroenterology, Humanitas Research Hospital)

  • Jo Spencer

    (King’s College London)

  • Manuel Rodriguez-Justo

    (Cancer Institute, University College London)

  • Francesca D. Ciccarelli

    (King’s College London)

Abstract

Synchronous colorectal cancers (syCRCs) are physically separated tumours that develop simultaneously. To understand how the genetic and environmental background influences the development of multiple tumours, here we conduct a comparative analysis of 20 syCRCs from 10 patients. We show that syCRCs have independent genetic origins, acquire dissimilar somatic alterations, and have different clone composition. This inter- and intratumour heterogeneity must be considered in the selection of therapy and in the monitoring of resistance. SyCRC patients show a higher occurrence of inherited damaging mutations in immune-related genes compared to patients with solitary colorectal cancer and to healthy individuals from the 1,000 Genomes Project. Moreover, they have a different composition of immune cell populations in tumour and normal mucosa, and transcriptional differences in immune-related biological processes. This suggests an environmental field effect that promotes multiple tumours likely in the background of inflammation.

Suggested Citation

  • Matteo Cereda & Gennaro Gambardella & Lorena Benedetti & Fabio Iannelli & Dominic Patel & Gianluca Basso & Rosalinda F. Guerra & Thanos P. Mourikis & Ignazio Puccio & Shruti Sinha & Luigi Laghi & Jo S, 2016. "Patients with genetically heterogeneous synchronous colorectal cancer carry rare damaging germline mutations in immune-related genes," Nature Communications, Nature, vol. 7(1), pages 1-12, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12072
    DOI: 10.1038/ncomms12072
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms12072
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms12072?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
    ---><---

    Citations

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


    Cited by:

    1. Marie-Julie Nokin & Alessia Mira & Enrico Patrucco & Biagio Ricciuti & Sophie Cousin & Isabelle Soubeyran & Sonia San José & Serena Peirone & Livia Caizzi & Sandra Vietti Michelina & Aurelien Bourdon , 2024. "RAS-ON inhibition overcomes clinical resistance to KRAS G12C-OFF covalent blockade," Nature Communications, Nature, vol. 15(1), pages 1-18, 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:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12072. 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.