IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-06027-1.html
   My bibliography  Save this article

The genomic landscape of cutaneous SCC reveals drivers and a novel azathioprine associated mutational signature

Author

Listed:
  • Gareth J. Inman

    (University of Dundee)

  • Jun Wang

    (Queen Mary University of London)

  • Ai Nagano

    (Queen Mary University of London)

  • Ludmil B. Alexandrov

    (University of California, San Diego)

  • Karin J. Purdie

    (Queen Mary University of London)

  • Richard G. Taylor

    (University of Dundee)

  • Victoria Sherwood

    (University of Dundee)

  • Jason Thomson

    (Queen Mary University of London)

  • Sarah Hogan

    (Queen Mary University of London)

  • Lindsay C. Spender

    (University of Dundee)

  • Andrew P. South

    (Thomas Jefferson University)

  • Michael Stratton

    (Cancer Genome Project, Wellcome Trust Sanger Institute)

  • Claude Chelala

    (Queen Mary University of London)

  • Catherine A. Harwood

    (Queen Mary University of London)

  • Charlotte M. Proby

    (University of Dundee)

  • Irene M. Leigh

    (University of Dundee)

Abstract

Cutaneous squamous cell carcinoma (cSCC) has a high tumour mutational burden (50 mutations per megabase DNA pair). Here, we combine whole-exome analyses from 40 primary cSCC tumours, comprising 20 well-differentiated and 20 moderately/poorly differentiated tumours, with accompanying clinical data from a longitudinal study of immunosuppressed and immunocompetent patients and integrate this analysis with independent gene expression studies. We identify commonly mutated genes, copy number changes and altered pathways and processes. Comparisons with tumour differentiation status suggest events which may drive disease progression. Mutational signature analysis reveals the presence of a novel signature (signature 32), whose incidence correlates with chronic exposure to the immunosuppressive drug azathioprine. Characterisation of a panel of 15 cSCC tumour-derived cell lines reveals that they accurately reflect the mutational signatures and genomic alterations of primary tumours and provide a valuable resource for the validation of tumour drivers and therapeutic targets.

Suggested Citation

  • Gareth J. Inman & Jun Wang & Ai Nagano & Ludmil B. Alexandrov & Karin J. Purdie & Richard G. Taylor & Victoria Sherwood & Jason Thomson & Sarah Hogan & Lindsay C. Spender & Andrew P. South & Michael S, 2018. "The genomic landscape of cutaneous SCC reveals drivers and a novel azathioprine associated mutational signature," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06027-1
    DOI: 10.1038/s41467-018-06027-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-06027-1
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-06027-1?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
    ---><---

    Citations

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


    Cited by:

    1. Peter Bailey & Rachel A. Ridgway & Patrizia Cammareri & Mairi Treanor-Taylor & Ulla-Maja Bailey & Christina Schoenherr & Max Bone & Daniel Schreyer & Karin Purdie & Jason Thomson & William Rickaby & R, 2023. "Driver gene combinations dictate cutaneous squamous cell carcinoma disease continuum progression," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Lucia Morgado-Palacin & Jessie A. Brown & Thomas F. Martinez & Juana M. Garcia-Pedrero & Farhad Forouhar & S. Aidan Quinn & Clara Reglero & Joan Vaughan & Yasamin Hajy Heydary & Cynthia Donaldson & Sa, 2023. "The TINCR ubiquitin-like microprotein is a tumor suppressor in squamous cell carcinoma," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    3. Annarita Nappi & Caterina Miro & Antonio Pezone & Alfonso Tramontano & Emery Cicco & Serena Sagliocchi & Annunziata Gaetana Cicatiello & Melania Murolo & Sepehr Torabinejad & Elena Abbotto & Giuseppin, 2023. "Loss of p53 activates thyroid hormone via type 2 deiodinase and enhances DNA damage," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    4. Máire Ní Leathlobhair & Anna Frangou & Ben Kinnersley & Alex J. Cornish & Daniel Chubb & Eszter Lakatos & Prabhu Arumugam & Andreas J. Gruber & Philip Law & Avraam Tapinos & G. Maria Jakobsdottir & Il, 2024. "Genomic landscape of adult testicular germ cell tumours in the 100,000 Genomes Project," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    5. Frederic Li Mow Chee & Bruno Beernaert & Billie G. C. Griffith & Alexander E. P. Loftus & Yatendra Kumar & Jimi C. Wills & Martin Lee & Jessica Valli & Ann P. Wheeler & J. Douglas Armstrong & Maddy Pa, 2023. "Mena regulates nesprin-2 to control actin–nuclear lamina associations, trans-nuclear membrane signalling and gene expression," Nature Communications, Nature, vol. 14(1), pages 1-19, 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:9:y:2018:i:1:d:10.1038_s41467-018-06027-1. 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.