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Whole-genome plasma sequencing reveals focal amplifications as a driving force in metastatic prostate cancer

Author

Listed:
  • Peter Ulz

    (Institute of Human Genetics, Medical University of Graz)

  • Jelena Belic

    (Institute of Human Genetics, Medical University of Graz)

  • Ricarda Graf

    (Institute of Human Genetics, Medical University of Graz)

  • Martina Auer

    (Institute of Human Genetics, Medical University of Graz)

  • Ingrid Lafer

    (Institute of Human Genetics, Medical University of Graz)

  • Katja Fischereder

    (Medical University of Graz)

  • Gerald Webersinke

    (Hospital Barmherzige Schwestern Linz)

  • Karl Pummer

    (Medical University of Graz)

  • Herbert Augustin

    (Medical University of Graz)

  • Martin Pichler

    (Medical University of Graz)

  • Gerald Hoefler

    (Institute of Pathology, Medical University of Graz)

  • Thomas Bauernhofer

    (Medical University of Graz)

  • Jochen B. Geigl

    (Institute of Human Genetics, Medical University of Graz)

  • Ellen Heitzer

    (Institute of Human Genetics, Medical University of Graz)

  • Michael R. Speicher

    (Institute of Human Genetics, Medical University of Graz)

Abstract

Genomic alterations in metastatic prostate cancer remain incompletely characterized. Here we analyse 493 prostate cancer cases from the TCGA database and perform whole-genome plasma sequencing on 95 plasma samples derived from 43 patients with metastatic prostate cancer. From these samples, we identify established driver aberrations in a cancer-related gene in nearly all cases (97.7%), including driver gene fusions (TMPRSS2:ERG), driver focal deletions (PTEN, RYBP and SHQ1) and driver amplifications (AR and MYC). In serial plasma analyses, we observe changes in focal amplifications in 40% of cases. The mean time interval between new amplifications was 26.4 weeks (range: 5–52 weeks), suggesting that they represent rapid adaptations to selection pressure. An increase in neuron-specific enolase is accompanied by clonal pattern changes in the tumour genome, most consistent with subclonal diversification of the tumour. Our findings suggest a high plasticity of prostate cancer genomes with newly occurring focal amplifications as a driving force in progression.

Suggested Citation

  • Peter Ulz & Jelena Belic & Ricarda Graf & Martina Auer & Ingrid Lafer & Katja Fischereder & Gerald Webersinke & Karl Pummer & Herbert Augustin & Martin Pichler & Gerald Hoefler & Thomas Bauernhofer & , 2016. "Whole-genome plasma sequencing reveals focal amplifications as a driving force in metastatic prostate cancer," Nature Communications, Nature, vol. 7(1), pages 1-12, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12008
    DOI: 10.1038/ncomms12008
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