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Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis

Author

Listed:
  • Katia Nones

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia
    QIMR Berghofer Medical Research Institute, Herston)

  • Nicola Waddell

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia
    QIMR Berghofer Medical Research Institute, Herston)

  • Nicci Wayte

    (Surgical Oncology Group, School of Medicine, The University of Queensland, Translational Research Institute at the Princess Alexandra Hospital, Woolloongabba)

  • Ann-Marie Patch

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia)

  • Peter Bailey

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia)

  • Felicity Newell

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia)

  • Oliver Holmes

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia
    QIMR Berghofer Medical Research Institute, Herston)

  • J. Lynn Fink

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia)

  • Michael C. J. Quinn

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia)

  • Yue Hang Tang

    (Surgical Oncology Group, School of Medicine, The University of Queensland, Translational Research Institute at the Princess Alexandra Hospital, Woolloongabba)

  • Guy Lampe

    (Princess Alexandra Hospital, Woolloongabba)

  • Kelly Quek

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia)

  • Kelly A. Loffler

    (Surgical Oncology Group, School of Medicine, The University of Queensland, Translational Research Institute at the Princess Alexandra Hospital, Woolloongabba)

  • Suzanne Manning

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia)

  • Senel Idrisoglu

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia)

  • David Miller

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia)

  • Qinying Xu

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia
    QIMR Berghofer Medical Research Institute, Herston)

  • Nick Waddell

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia)

  • Peter J. Wilson

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia)

  • Timothy J. C. Bruxner

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia)

  • Angelika N. Christ

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia)

  • Ivon Harliwong

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia)

  • Craig Nourse

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia)

  • Ehsan Nourbakhsh

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia)

  • Matthew Anderson

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia)

  • Stephen Kazakoff

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia)

  • Conrad Leonard

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia
    QIMR Berghofer Medical Research Institute, Herston)

  • Scott Wood

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia
    QIMR Berghofer Medical Research Institute, Herston)

  • Peter T. Simpson

    (QIMR Berghofer Medical Research Institute, Herston
    The University of Queensland, UQ Centre for Clinical Research, Herston
    The University of Queensland, School of Medicine)

  • Lynne E. Reid

    (QIMR Berghofer Medical Research Institute, Herston
    The University of Queensland, UQ Centre for Clinical Research, Herston)

  • Lutz Krause

    (QIMR Berghofer Medical Research Institute, Herston)

  • Damian J. Hussey

    (Flinders Medical Centre)

  • David I. Watson

    (Flinders Medical Centre)

  • Reginald V. Lord

    (St Vincent’s Centre for Applied Medical Research, University of Notre Dame and University of New South Wales)

  • Derek Nancarrow

    (QIMR Berghofer Medical Research Institute, Herston)

  • Wayne A. Phillips

    (Peter MacCallum Cancer Centre)

  • David Gotley

    (School of Medicine, The University of Queensland, Princess Alexandra Hospital, Woolloongabba)

  • B. Mark Smithers

    (School of Medicine, The University of Queensland, Princess Alexandra Hospital, Woolloongabba)

  • David C. Whiteman

    (QIMR Berghofer Medical Research Institute, Herston)

  • Nicholas K. Hayward

    (QIMR Berghofer Medical Research Institute, Herston)

  • Peter J. Campbell

    (Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton)

  • John V. Pearson

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia
    QIMR Berghofer Medical Research Institute, Herston)

  • Sean M. Grimmond

    (Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia
    Wolfson Wohl Cancer Research Centre, Institute for Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK)

  • Andrew P. Barbour

    (Surgical Oncology Group, School of Medicine, The University of Queensland, Translational Research Institute at the Princess Alexandra Hospital, Woolloongabba
    School of Medicine, The University of Queensland, Princess Alexandra Hospital, Woolloongabba)

Abstract

Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC.

Suggested Citation

  • Katia Nones & Nicola Waddell & Nicci Wayte & Ann-Marie Patch & Peter Bailey & Felicity Newell & Oliver Holmes & J. Lynn Fink & Michael C. J. Quinn & Yue Hang Tang & Guy Lampe & Kelly Quek & Kelly A. L, 2014. "Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis," Nature Communications, Nature, vol. 5(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6224
    DOI: 10.1038/ncomms6224
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    Cited by:

    1. Marjan M. Naeini & Felicity Newell & Lauren G. Aoude & Vanessa F. Bonazzi & Kalpana Patel & Guy Lampe & Lambros T. Koufariotis & Vanessa Lakis & Venkateswar Addala & Olga Kondrashova & Rebecca L. John, 2023. "Multi-omic features of oesophageal adenocarcinoma in patients treated with preoperative neoadjuvant therapy," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Chunyang Bao & Richard W. Tourdot & Gregory J. Brunette & Chip Stewart & Lili Sun & Hideo Baba & Masayuki Watanabe & Agoston T. Agoston & Kunal Jajoo & Jon M. Davison & Katie S. Nason & Gad Getz & Ken, 2023. "Genomic signatures of past and present chromosomal instability in Barrett’s esophagus and early esophageal adenocarcinoma," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    3. Thomas G. Paulson & Patricia C. Galipeau & Kenji M. Oman & Carissa A. Sanchez & Mary K. Kuhner & Lucian P. Smith & Kevin Hadi & Minita Shah & Kanika Arora & Jennifer Shelton & Molly Johnson & Andre Co, 2022. "Somatic whole genome dynamics of precancer in Barrett’s esophagus reveals features associated with disease progression," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. A. C. Katz-Summercorn & S. Jammula & A. Frangou & I. Peneva & M. O’Donovan & M. Tripathi & S. Malhotra & M. Pietro & S. Abbas & G. Devonshire & W. Januszewicz & A. Blasko & K. Nowicki-Osuch & S. MacRa, 2022. "Multi-omic cross-sectional cohort study of pre-malignant Barrett’s esophagus reveals early structural variation and retrotransposon activity," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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