Whole-genome plasma sequencing reveals focal amplifications as a driving force in metastatic prostate cancer
| Autor: | Thomas Bauernhofer, Ellen Heitzer, Ricarda Graf, Gerald Hoefler, Karl Pummer, Gerald Webersinke, Ingrid Lafer, Martina Auer, Katja Fischereder, Michael R. Speicher, H. Augustin, Jelena Belic, Martin Pichler, Jochen B. Geigl, Peter Ulz |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Science Biopsy Gene Dosage General Physics and Astronomy Bioinformatics Genome Gene dosage TMPRSS2 Article General Biochemistry Genetics and Molecular Biology Proto-Oncogene Proteins c-myc 03 medical and health sciences Prostate cancer 0302 clinical medicine medicine Cluster Analysis Humans PTEN ddc:610 Neoplasm Metastasis Chromosome Aberrations Multidisciplinary biology Genome Human Prostatic Neoplasms Cell Differentiation DNA Neoplasm Sequence Analysis DNA General Chemistry Prostate-Specific Antigen medicine.disease 3. Good health Prostate-specific antigen 030104 developmental biology 030220 oncology & carcinogenesis Disease Progression biology.protein Cancer research Human genome Erg Gene Deletion |
| Zdroj: | Nature Communications Nature Communications, Vol 7, Iss 1, Pp 1-12 (2016) |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/ncomms12008 |
| Popis: | 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. The genomic features of metastatic prostate cancer are beginning to be understood. Here, the authors performed whole genome sequencing of plasma samples from these patients and found a high plasticity of the cancer genomes with newly occurring focal amplifications as a driving force in progression. |
| Databáze: | OpenAIRE |
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