IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-04322-5.html
   My bibliography  Save this article

Outlier response to anti-PD1 in uveal melanoma reveals germline MBD4 mutations in hypermutated tumors

Author

Listed:
  • Manuel Rodrigues

    (PSL Research University, INSERM U830, DNA Repair and Uveal Melanoma (D.R.U.M.), Equipe labellisée par la Ligue Nationale contre le Cancer
    PSL Research University)

  • Lenha Mobuchon

    (PSL Research University, INSERM U830, DNA Repair and Uveal Melanoma (D.R.U.M.), Equipe labellisée par la Ligue Nationale contre le Cancer)

  • Alexandre Houy

    (PSL Research University, INSERM U830, DNA Repair and Uveal Melanoma (D.R.U.M.), Equipe labellisée par la Ligue Nationale contre le Cancer)

  • Alice Fiévet

    (PSL Research University, INSERM U830, DNA Repair and Uveal Melanoma (D.R.U.M.), Equipe labellisée par la Ligue Nationale contre le Cancer
    PSL Research University)

  • Sophie Gardrat

    (PSL Research University)

  • Raymond L. Barnhill

    (PSL Research University
    University of Paris Descartes)

  • Tatiana Popova

    (PSL Research University, INSERM U830, DNA Repair and Uveal Melanoma (D.R.U.M.), Equipe labellisée par la Ligue Nationale contre le Cancer)

  • Vincent Servois

    (PSL Research University)

  • Aurore Rampanou

    (PSL Research University, Laboratory of Circulating Tumor Biomarkers, SiRIC)

  • Aurore Mouton

    (PSL Research University, INSERM CIC-BT 1428)

  • Stéphane Dayot

    (PSL Research University, INSERM U830, DNA Repair and Uveal Melanoma (D.R.U.M.), Equipe labellisée par la Ligue Nationale contre le Cancer)

  • Virginie Raynal

    (PSL Research University, INSERM U830 and Institut Curie Genomics of Excellence (ICGex) Platform)

  • Michèle Galut

    (PSL Research University, Biological Resource Center)

  • Marc Putterman

    (Quinze-Vingts National Ophthalmology Hospital)

  • Sarah Tick

    (Quinze-Vingts National Ophthalmology Hospital)

  • Nathalie Cassoux

    (University of Paris Descartes
    PSL Research University)

  • Sergio Roman-Roman

    (PSL Research University)

  • François-Clément Bidard

    (PSL Research University
    PSL Research University, Laboratory of Circulating Tumor Biomarkers, SiRIC
    Paris Saclay University)

  • Olivier Lantz

    (PSL Research University, INSERM CIC-BT 1428)

  • Pascale Mariani

    (PSL Research University)

  • Sophie Piperno-Neumann

    (PSL Research University)

  • Marc-Henri Stern

    (PSL Research University, INSERM U830, DNA Repair and Uveal Melanoma (D.R.U.M.), Equipe labellisée par la Ligue Nationale contre le Cancer
    PSL Research University)

Abstract

Metastatic uveal melanoma is a deadly disease with no proven standard of care. Here we present a metastatic uveal melanoma patient with an exceptional high sensitivity to a PD-1 inhibitor associated with outlier CpG>TpG mutation burden, MBD4 germline deleterious mutation, and somatic MBD4 inactivation in the tumor. We identify additional tumors in The Cancer Genome Atlas (TCGA) cohorts with similar hypermutator profiles in patients carrying germline deleterious MBD4 mutations and somatic loss of heterozygosity. This MBD4-related hypermutator phenotype may explain unexpected responses to immune checkpoint inhibitors.

Suggested Citation

  • Manuel Rodrigues & Lenha Mobuchon & Alexandre Houy & Alice Fiévet & Sophie Gardrat & Raymond L. Barnhill & Tatiana Popova & Vincent Servois & Aurore Rampanou & Aurore Mouton & Stéphane Dayot & Virgini, 2018. "Outlier response to anti-PD1 in uveal melanoma reveals germline MBD4 mutations in hypermutated tumors," Nature Communications, Nature, vol. 9(1), pages 1-6, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04322-5
    DOI: 10.1038/s41467-018-04322-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-04322-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-04322-5?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. Mischan Vali-Pour & Solip Park & Jose Espinosa-Carrasco & Daniel Ortiz-Martínez & Ben Lehner & Fran Supek, 2022. "The impact of rare germline variants on human somatic mutation processes," Nature Communications, Nature, vol. 13(1), pages 1-21, 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_s41467-018-04322-5. 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.