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Genomic landscape of platinum resistant and sensitive testicular cancers

Author

Listed:
  • Chey Loveday

    (The Institute of Cancer Research)

  • Kevin Litchfield

    (The Institute of Cancer Research
    University College London Cancer Institute)

  • Paula Z. Proszek

    (The Royal Marsden NHS Trust)

  • Alex J. Cornish

    (The Institute of Cancer Research)

  • Flavia Santo

    (The Royal Marsden NHS Trust)

  • Max Levy

    (The Institute of Cancer Research)

  • Geoff Macintyre

    (University of Cambridge)

  • Amy Holryod

    (The Institute of Cancer Research)

  • Peter Broderick

    (The Institute of Cancer Research)

  • Darshna Dudakia

    (The Institute of Cancer Research)

  • Barbara Benton

    (The Institute of Cancer Research)

  • Maise Al Bakir

    (University College London Cancer Institute)

  • Crispin Hiley

    (University College London Cancer Institute)

  • Emily Grist

    (The Institute of Cancer Research)

  • Charles Swanton

    (University College London Cancer Institute
    UCL Cancer Institute
    UCL Cancer Institute)

  • Robert Huddart

    (Institute of Cancer Research)

  • Tom Powles

    (Queen Mary University)

  • Simon Chowdhury

    (Guys and St Thomas’ NHS Foundation Trust)

  • Janet Shipley

    (The Institute of Cancer Research
    The Institute of Cancer Research)

  • Simon O’Connor

    (The Royal Marsden NHS Trust
    Addenbrooke’s Hospital
    University of Cambridge)

  • James D. Brenton

    (University of Cambridge)

  • Alison Reid

    (The Royal Marsden NHS Foundation Trust)

  • David Gonzalez Castro

    (Queen’s University Belfast)

  • Richard S. Houlston

    (The Institute of Cancer Research
    The Institute of Cancer Research)

  • Clare Turnbull

    (The Institute of Cancer Research
    Queen Mary University
    Great Maze Pond
    National Cancer Registration and Analysis Service)

Abstract

While most testicular germ cell tumours (TGCTs) exhibit exquisite sensitivity to platinum chemotherapy, ~10% are platinum resistant. To gain insight into the underlying mechanisms, we undertake whole exome sequencing and copy number analysis in 40 tumours from 26 cases with platinum-resistant TGCT, and combine this with published genomic data on an additional 624 TGCTs. We integrate analyses for driver mutations, mutational burden, global, arm-level and focal copy number (CN) events, and SNV and CN signatures. Albeit preliminary and observational in nature, these analyses provide support for a possible mechanistic link between early driver mutations in RAS and KIT and the widespread copy number events by which TGCT is characterised.

Suggested Citation

  • Chey Loveday & Kevin Litchfield & Paula Z. Proszek & Alex J. Cornish & Flavia Santo & Max Levy & Geoff Macintyre & Amy Holryod & Peter Broderick & Darshna Dudakia & Barbara Benton & Maise Al Bakir & C, 2020. "Genomic landscape of platinum resistant and sensitive testicular cancers," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15768-x
    DOI: 10.1038/s41467-020-15768-x
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    Cited by:

    1. 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.
    2. Thomas R. W. Oliver & Lia Chappell & Rashesh Sanghvi & Lauren Deighton & Naser Ansari-Pour & Stefan C. Dentro & Matthew D. Young & Tim H. H. Coorens & Hyunchul Jung & Tim Butler & Matthew D. C. Nevill, 2022. "Clonal diversification and histogenesis of malignant germ cell tumours," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

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