IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-21576-8.html
   My bibliography  Save this article

Evolution of late-stage metastatic melanoma is dominated by aneuploidy and whole genome doubling

Author

Listed:
  • Ismael A. Vergara

    (Walter and Eliza Hall Institute of Medical Research
    Peter MacCallum Cancer Centre
    Melanoma Institute of Australia)

  • Christopher P. Mintoff

    (Peter MacCallum Cancer Centre)

  • Shahneen Sandhu

    (Peter MacCallum Cancer Centre)

  • Lachlan McIntosh

    (Walter and Eliza Hall Institute of Medical Research
    The University of Melbourne)

  • Richard J. Young

    (Peter MacCallum Cancer Centre)

  • Stephen Q. Wong

    (Peter MacCallum Cancer Centre)

  • Andrew Colebatch

    (Peter MacCallum Cancer Centre)

  • Daniel L. Cameron

    (Walter and Eliza Hall Institute of Medical Research
    The University of Melbourne)

  • Julia Lai Kwon

    (Peter MacCallum Cancer Centre)

  • Rory Wolfe

    (Monash University)

  • Angela Peng

    (Peter MacCallum Cancer Centre
    Nursing and Health Sciences, Monash University)

  • Jason Ellul

    (Peter MacCallum Cancer Centre)

  • Xuelin Dou

    (Peter MacCallum Cancer Centre)

  • Clare Fedele

    (Peter MacCallum Cancer Centre)

  • Samantha Boyle

    (Peter MacCallum Cancer Centre)

  • Gisela Mir Arnau

    (Peter MacCallum Cancer Centre)

  • Jeanette Raleigh

    (Peter MacCallum Cancer Centre)

  • Athena Hatzimihalis

    (Peter MacCallum Cancer Centre)

  • Pacman Szeto

    (Peter MacCallum Cancer Centre
    Nursing and Health Sciences, Monash University)

  • Jennifer Mooi

    (Peter MacCallum Cancer Centre)

  • Daniel S. Widmer

    (University of Zürich Hospital)

  • Phil F. Cheng

    (University of Zürich Hospital)

  • Valerie Amann

    (University of Zürich Hospital)

  • Reinhard Dummer

    (University of Zürich Hospital)

  • Nicholas Hayward

    (Melanoma Institute of Australia
    QIMR Berghofer Medical Research Institute)

  • James Wilmott

    (Melanoma Institute of Australia)

  • Richard A. Scolyer

    (Melanoma Institute of Australia
    Royal Prince Alfred Hospital
    The University of Sydney)

  • Raymond J. Cho

    (University of California)

  • David Bowtell

    (Peter MacCallum Cancer Centre
    The University of Melbourne)

  • Heather Thorne

    (Peter MacCallum Cancer Centre)

  • Kathryn Alsop

    (Peter MacCallum Cancer Centre)

  • Stephen Cordner

    (The Victorian Institute of Forensic Medicine)

  • Noel Woodford

    (The Victorian Institute of Forensic Medicine)

  • Jodie Leditschke

    (The Victorian Institute of Forensic Medicine)

  • Patricia O’Brien

    (The Victorian Institute of Forensic Medicine)

  • Sarah-Jane Dawson

    (Peter MacCallum Cancer Centre
    The University of Melbourne)

  • Grant A. McArthur

    (Peter MacCallum Cancer Centre
    The University of Melbourne)

  • Graham J. Mann

    (Melanoma Institute of Australia
    University of Sydney)

  • Mitchell P. Levesque

    (University of Zürich Hospital)

  • Anthony T. Papenfuss

    (Walter and Eliza Hall Institute of Medical Research
    Peter MacCallum Cancer Centre
    The University of Melbourne
    The University of Melbourne)

  • Mark Shackleton

    (Peter MacCallum Cancer Centre
    Nursing and Health Sciences, Monash University
    The University of Melbourne
    Alfred Health)

Abstract

Although melanoma is initiated by acquisition of point mutations and limited focal copy number alterations in melanocytes-of-origin, the nature of genetic changes that characterise lethal metastatic disease is poorly understood. Here, we analyze the evolution of human melanoma progressing from early to late disease in 13 patients by sampling their tumours at multiple sites and times. Whole exome and genome sequencing data from 88 tumour samples reveals only limited gain of point mutations generally, with net mutational loss in some metastases. In contrast, melanoma evolution is dominated by whole genome doubling and large-scale aneuploidy, in which widespread loss of heterozygosity sculpts the burden of point mutations, neoantigens and structural variants even in treatment-naïve and primary cutaneous melanomas in some patients. These results imply that dysregulation of genomic integrity is a key driver of selective clonal advantage during melanoma progression.

Suggested Citation

  • Ismael A. Vergara & Christopher P. Mintoff & Shahneen Sandhu & Lachlan McIntosh & Richard J. Young & Stephen Q. Wong & Andrew Colebatch & Daniel L. Cameron & Julia Lai Kwon & Rory Wolfe & Angela Peng , 2021. "Evolution of late-stage metastatic melanoma is dominated by aneuploidy and whole genome doubling," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21576-8
    DOI: 10.1038/s41467-021-21576-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-21576-8
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-021-21576-8?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. Rong Xiao & Deshu Xu & Meili Zhang & Zhanghua Chen & Li Cheng & Songjie Du & Mingfei Lu & Tonghai Zhou & Ruoyan Li & Fan Bai & Yue Huang, 2024. "Aneuploid embryonic stem cells drive teratoma metastasis," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Philip Smith & Thomas Bradley & Lena Morrill Gavarró & Teodora Goranova & Darren P. Ennis & Hasan B. Mirza & Dilrini Silva & Anna M. Piskorz & Carolin M. Sauer & Sarwah Al-Khalidi & Ionut-Gabriel Funi, 2023. "The copy number and mutational landscape of recurrent ovarian high-grade serous carcinoma," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Revati Darp & Marc A. Vittoria & Neil J. Ganem & Craig J. Ceol, 2022. "Oncogenic BRAF induces whole-genome doubling through suppression of cytokinesis," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. Marc A. Vittoria & Nathan Kingston & Kristyna Kotynkova & Eric Xia & Rui Hong & Lee Huang & Shayna McDonald & Andrew Tilston-Lunel & Revati Darp & Joshua D. Campbell & Deborah Lang & Xiaowei Xu & Crai, 2022. "Inactivation of the Hippo tumor suppressor pathway promotes melanoma," Nature Communications, Nature, vol. 13(1), pages 1-17, 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:12:y:2021:i:1:d:10.1038_s41467-021-21576-8. 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.