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Multi-site clonality analysis uncovers pervasive heterogeneity across melanoma metastases

Author

Listed:
  • Roy Rabbie

    (Experimental Cancer Genetics, The Wellcome Sanger Institute
    Cambridge University Hospitals NHS Foundation Trust)

  • Naser Ansari-Pour

    (University of Oxford)

  • Oliver Cast

    (University of Cambridge, Li Ka Shing Centre)

  • Doreen Lau

    (University of Cambridge)

  • Francis Scott

    (University of Cambridge)

  • Sarah J. Welsh

    (Cambridge University Hospitals NHS Foundation Trust)

  • Christine Parkinson

    (Cambridge University Hospitals NHS Foundation Trust)

  • Leila Khoja

    (University of Birmingham)

  • Luiza Moore

    (The Cancer, Ageing and Somatic Mutation Programme, Wellcome Sanger Institute
    Cambridge University Hospitals NHS Foundation Trust)

  • Mark Tullett

    (St Richard’s Hospital, Spitalfield Lane)

  • Kim Wong

    (Experimental Cancer Genetics, The Wellcome Sanger Institute)

  • Ingrid Ferreira

    (Experimental Cancer Genetics, The Wellcome Sanger Institute)

  • Julia M. Martínez Gómez

    (University of Zurich, University of Zurich Hospital)

  • Mitchell Levesque

    (University of Zurich, University of Zurich Hospital)

  • Ferdia A. Gallagher

    (University of Cambridge)

  • Alejandro Jiménez-Sánchez

    (University of Cambridge, Li Ka Shing Centre)

  • Laura Riva

    (Experimental Cancer Genetics, The Wellcome Sanger Institute)

  • Martin L. Miller

    (University of Cambridge, Li Ka Shing Centre)

  • Kieren Allinson

    (Cambridge University Hospitals NHS Foundation Trust)

  • Peter J. Campbell

    (The Cancer, Ageing and Somatic Mutation Programme, Wellcome Sanger Institute)

  • Pippa Corrie

    (Cambridge University Hospitals NHS Foundation Trust)

  • David C. Wedge

    (University of Oxford
    Oxford NIHR Biomedical Research Centre
    University of Manchester)

  • David J. Adams

    (Experimental Cancer Genetics, The Wellcome Sanger Institute)

Abstract

Metastatic melanoma carries a poor prognosis despite modern systemic therapies. Understanding the evolution of the disease could help inform patient management. Through whole-genome sequencing of 13 melanoma metastases sampled at autopsy from a treatment naïve patient and by leveraging the analytical power of multi-sample analyses, we reveal evidence of diversification among metastatic lineages. UV-induced mutations dominate the trunk, whereas APOBEC-associated mutations are found in the branches of the evolutionary tree. Multi-sample analyses from a further seven patients confirmed that lineage diversification was pervasive, representing an important mode of melanoma dissemination. Our analyses demonstrate that joint analysis of cancer cell fraction estimates across multiple metastases can uncover previously unrecognised levels of tumour heterogeneity and highlight the limitations of inferring heterogeneity from a single biopsy.

Suggested Citation

  • Roy Rabbie & Naser Ansari-Pour & Oliver Cast & Doreen Lau & Francis Scott & Sarah J. Welsh & Christine Parkinson & Leila Khoja & Luiza Moore & Mark Tullett & Kim Wong & Ingrid Ferreira & Julia M. Mart, 2020. "Multi-site clonality analysis uncovers pervasive heterogeneity across melanoma metastases," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18060-0
    DOI: 10.1038/s41467-020-18060-0
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    Cited by:

    1. 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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