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

Peter Ulz, Jelena Belic, Ricarda Graf, Martina Auer, Ingrid Lafer, Katja Fischereder, Gerald Webersinke, Karl Pummer, Herbert Augustin, Martin Pichler, Gerald Hoefler, Thomas Bauernhofer, Jochen B. Geigl, Ellen Heitzer () and Michael R. Speicher
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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

Nature Communications, 2016, vol. 7, issue 1, 1-12

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms12008

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