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

P Ulz, J Belic, R Graf, M Auer, I Lafer… - Nature …, 2016 - nature.com
P Ulz, J Belic, R Graf, M Auer, I Lafer, K Fischereder, G Webersinke, K Pummer, H Augustin…
Nature communications, 2016nature.com
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 …
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.
nature.com