IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-59661-x.html
   My bibliography  Save this article

Whole genome sequencing improves tissue-of-origin diagnosis and treatment options for cancer of unknown primary

Author

Listed:
  • Richard J. Rebello

    (University of Melbourne
    University of Melbourne)

  • Atara Posner

    (University of Melbourne
    University of Melbourne)

  • Ruining Dong

    (University of Melbourne
    University of Melbourne)

  • Owen W. J. Prall

    (Peter MacCallum Cancer Centre)

  • Tharani Sivakumaran

    (Peter MacCallum Cancer Centre
    University of Melbourne)

  • Camilla B. Mitchell

    (University of Melbourne
    University of Melbourne)

  • Aidan Flynn

    (University of Melbourne
    University of Melbourne)

  • Alex Caneborg

    (University of Melbourne
    University of Melbourne)

  • Catherine Mitchell

    (Peter MacCallum Cancer Centre
    University of Melbourne)

  • Sehrish Kanwal

    (University of Melbourne
    University of Melbourne)

  • Clare Fedele

    (University of Melbourne
    University of Melbourne)

  • Samantha Webb

    (Peter MacCallum Cancer Centre)

  • Krista Fisher

    (Peter MacCallum Cancer Centre)

  • Hui-Li Wong

    (Peter MacCallum Cancer Centre
    University of Melbourne)

  • Shiva Balachander

    (Peter MacCallum Cancer Centre)

  • Wenying Zhu

    (University of Melbourne
    University of Melbourne)

  • Shannon Nicolson

    (University of Melbourne
    University of Melbourne)

  • Voula Dimitriadis

    (University of Melbourne)

  • Nicholas Wilcken

    (The Westmead Institute for Medical Research)

  • Anna DeFazio

    (The Westmead Institute for Medical Research
    Westmead Hospital
    The University of Sydney, a joint venture with Cancer Council NSW)

  • Bo Gao

    (Westmead Hospital)

  • Madhu Singh

    (Barwon Health Cancer Services)

  • Ian M. Collins

    (Warrnambool and Deakin University)

  • Christopher Steer

    (Rural Clinical Campus)

  • Mark Warren

    (Bendigo Health)

  • Narayan Karanth

    (Alan Walker Cancer Centre)

  • Huiling Xu

    (Peter MacCallum Cancer Centre)

  • Andrew Fellowes

    (Peter MacCallum Cancer Centre)

  • Rodney J. Hicks

    (University of Melbourne)

  • Kym Pham Stewart

    (University of Melbourne)

  • Charles Shale

    (Hartwig Medical Foundation)

  • Peter Priestley

    (Hartwig Medical Foundation)

  • Sarah-Jane Dawson

    (University of Melbourne
    University of Melbourne
    Peter MacCallum Cancer Centre)

  • Joseph H. A. Vissers

    (University of Melbourne
    University of Melbourne)

  • Stephen B. Fox

    (Peter MacCallum Cancer Centre
    University of Melbourne)

  • Penelope Schofield

    (University of Melbourne
    Swinburne University
    La Trobe University)

  • David Bowtell

    (University of Melbourne
    Peter MacCallum Cancer Centre)

  • Oliver Hofmann

    (University of Melbourne
    University of Melbourne)

  • Sean M. Grimmond

    (University of Melbourne)

  • Linda Mileshkin

    (Peter MacCallum Cancer Centre
    University of Melbourne
    Peter MacCallum Cancer Centre)

  • Richard W. Tothill

    (University of Melbourne
    University of Melbourne
    University of Melbourne)

Abstract

Genomics can inform both tissue-of-origin (TOO) and precision treatments for patients with cancer of unknown primary (CUP). Here, we use whole genome and transcriptome sequencing (WGTS) for 72 patients and show diagnostic superiority of WGTS over panel testing (386–523 genes) in 71 paired cases. WGTS detects all reportable DNA features found by panel as well as additional mutations of diagnostic or therapeutic relevance in 76% of cases. Curated WGTS features and a CUP prediction algorithm (CUPPA) trained on WGTS data of known cancer types informs TOO in 71% of cases otherwise undiagnosed by clinicopathology review. WGTS informs treatments for 79% of patients, compared to 59% by panel testing. Finally, WGS of cell-free DNA (cfDNA) from patients with a high cfDNA tumour fraction (>7%), enables high-likelihood CUPPA predictions in 41% of cases. WGTS is therefore superior to panel testing, broadens treatment options, and is feasible using routine pathology samples and cfDNA.

Suggested Citation

  • Richard J. Rebello & Atara Posner & Ruining Dong & Owen W. J. Prall & Tharani Sivakumaran & Camilla B. Mitchell & Aidan Flynn & Alex Caneborg & Catherine Mitchell & Sehrish Kanwal & Clare Fedele & Sam, 2025. "Whole genome sequencing improves tissue-of-origin diagnosis and treatment options for cancer of unknown primary," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59661-x
    DOI: 10.1038/s41467-025-59661-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-59661-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-59661-x?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
    ---><---

    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:16:y:2025:i:1:d:10.1038_s41467-025-59661-x. 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.