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We are analyzing https://link.springer.com/article/10.1186/gm434.

Title:
Tumor-associated copy number changes in the circulation of patients with prostate cancer identified through whole-genome sequencing | Genome Medicine
Description:
Background Patients with prostate cancer may present with metastatic or recurrent disease despite initial curative treatment. The propensity of metastatic prostate cancer to spread to the bone has limited repeated sampling of tumor deposits. Hence, considerably less is understood about this lethal metastatic disease, as it is not commonly studied. Here we explored whole-genome sequencing of plasma DNA to scan the tumor genomes of these patients non-invasively. Methods We wanted to make whole-genome analysis from plasma DNA amenable to clinical routine applications and developed an approach based on a benchtop high-throughput platform, that is, Illuminas MiSeq instrument. We performed whole-genome sequencing from plasma at a shallow sequencing depth to establish a genome-wide copy number profile of the tumor at low costs within 2 days. In parallel, we sequenced a panel of 55 high-interest genes and 38 introns with frequent fusion breakpoints such as the TMPRSS2-ERG fusion with high coverage. After intensive testing of our approach with samples from 25 individuals without cancer we analyzed 13 plasma samples derived from five patients with castration resistant (CRPC) and four patients with castration sensitive prostate cancer (CSPC). Results The genome-wide profiling in the plasma of our patients revealed multiple copy number aberrations including those previously reported in prostate tumors, such as losses in 8p and gains in 8q. High-level copy number gains in the AR locus were observed in patients with CRPC but not with CSPC disease. We identified the TMPRSS2-ERG rearrangement associated 3-Mbp deletion on chromosome 21 and found corresponding fusion plasma fragments in these cases. In an index case multiregional sequencing of the primary tumor identified different copy number changes in each sector, suggesting multifocal disease. Our plasma analyses of this index case, performed 13 years after resection of the primary tumor, revealed novel chromosomal rearrangements, which were stable in serial plasma analyses over a 9-month period, which is consistent with the presence of one metastatic clone. Conclusions The genomic landscape of prostate cancer can be established by non-invasive means from plasma DNA. Our approach provides specific genomic signatures within 2 days which may therefore serve as
Website Age:
28 years and 1 months (reg. 1997-05-29).

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Custom-built

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🌠 Phenomenal Traffic: 5M - 10M visitors per month


Based on our best estimate, this website will receive around 7,642,828 visitors per month in the current month.

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Keywords {πŸ”}

cancer, plasma, prostate, pubmed, sequencing, dna, article, crpc, tumor, patients, google, scholar, cspc, cas, samples, number, copy, analysis, zscores, approach, central, figure, analyses, genome, disease, file, plasmaseq, data, approximately, regions, performed, zscore, genomewide, additional, metastatic, genes, mbp, controls, wholegenome, previously, chromosome, cases, mutations, obtained, blood, reads, clinical, panel, cells, identified,

Topics {βœ’οΈ}

org/cancergenomics/prostate/data/mskcc_pca_segmented_copy-number uk/genetics/cgp/cosmic/ http increased genome-wide z-score gc-corrected read-count ratios tmprss2-erg-negative prostate cancers article download pdf tmprss2-erg-positive prostate cancers segmented dna-copy-number data benchtop high-throughput platform calculated gene-specific z-scores theresa benezeder androgen-receptor signaling axis european genome-phenome archive genome-wide z-score genome-wide z- score genome-wide z-scores z-score calculation microvortex-generating herringbone-chip tumor-specific copy number array-cgh profiles show blood copy-number signatures reliable copy-number measurements gene-specific z-scores distinguishing tmprss2-erg-positive akt-inactivating phosphatase phlpp1 androgen receptor gene cross-validated z-scores de bono js cell-free nucleic acids ar copy-number status castration-resistant prostate cancer androgen receptor signaling copy number profiles high-throughput sequencing data copy number profile array-cgh array-cgh par-masked hg19 genome simulated copy-number analyses cancer-specific genomic rearrangements published ctc-based studies copy number aberrations ets gene fusions large-scale sequencing projects counted high-quality alignments open-source package calculated 'segmental z-scores' clinic search search array-cgh profiles array-cgh profile identical copy number

Questions {❓}

  • Albertsen PC: Treatment of localized prostate cancer: when is active surveillance appropriate?

Schema {πŸ—ΊοΈ}

WebPage:
      mainEntity:
         headline:Tumor-associated copy number changes in the circulation of patients with prostate cancer identified through whole-genome sequencing
         description:Patients with prostate cancer may present with metastatic or recurrent disease despite initial curative treatment. The propensity of metastatic prostate cancer to spread to the bone has limited repeated sampling of tumor deposits. Hence, considerably less is understood about this lethal metastatic disease, as it is not commonly studied. Here we explored whole-genome sequencing of plasma DNA to scan the tumor genomes of these patients non-invasively. We wanted to make whole-genome analysis from plasma DNA amenable to clinical routine applications and developed an approach based on a benchtop high-throughput platform, that is, Illuminas MiSeq instrument. We performed whole-genome sequencing from plasma at a shallow sequencing depth to establish a genome-wide copy number profile of the tumor at low costs within 2 days. In parallel, we sequenced a panel of 55 high-interest genes and 38 introns with frequent fusion breakpoints such as the TMPRSS2-ERG fusion with high coverage. After intensive testing of our approach with samples from 25 individuals without cancer we analyzed 13 plasma samples derived from five patients with castration resistant (CRPC) and four patients with castration sensitive prostate cancer (CSPC). The genome-wide profiling in the plasma of our patients revealed multiple copy number aberrations including those previously reported in prostate tumors, such as losses in 8p and gains in 8q. High-level copy number gains in the AR locus were observed in patients with CRPC but not with CSPC disease. We identified the TMPRSS2-ERG rearrangement associated 3-Mbp deletion on chromosome 21 and found corresponding fusion plasma fragments in these cases. In an index case multiregional sequencing of the primary tumor identified different copy number changes in each sector, suggesting multifocal disease. Our plasma analyses of this index case, performed 13 years after resection of the primary tumor, revealed novel chromosomal rearrangements, which were stable in serial plasma analyses over a 9-month period, which is consistent with the presence of one metastatic clone. The genomic landscape of prostate cancer can be established by non-invasive means from plasma DNA. Our approach provides specific genomic signatures within 2 days which may therefore serve as 'liquid biopsy'.
         datePublished:2013-04-05T00:00:00Z
         dateModified:2013-04-05T00:00:00Z
         pageStart:1
         pageEnd:16
         license:http://creativecommons.org/licenses/by/2.0/
         sameAs:https://doi.org/10.1186/gm434
         keywords:
            Prostate Cancer
            Androgen Receptor
            Metastatic Prostate Cancer
            Copy Number Change
            Copy Number Aberration
            Human Genetics
            Metabolomics
            Bioinformatics
            Medicine/Public Health
            general
            Cancer Research
            Systems Biology
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            name:Genome Medicine
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                        name:Institute of Human Genetics, Medical University of Graz, Graz, Austria
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               name:Peter Ulz
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                        name:Institute of Human Genetics, Medical University of Graz, Graz, Austria
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               name:Franz Quehenberger
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                        name:Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria
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                        name:Institute of Human Genetics, Medical University of Graz, Graz, Austria
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                        name:Institute of Pathology, Medical University of Graz, Graz, Austria
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               name:Martin Haeusler
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                        name:Department of Obstetrics and Gynecology, Medical University of Graz, Graz, Austria
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                        name:Institute of Human Genetics, Medical University of Graz, Graz, Austria
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                        name:Institute of Human Genetics, Medical University of Graz, Graz, Austria
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ScholarlyArticle:
      headline:Tumor-associated copy number changes in the circulation of patients with prostate cancer identified through whole-genome sequencing
      description:Patients with prostate cancer may present with metastatic or recurrent disease despite initial curative treatment. The propensity of metastatic prostate cancer to spread to the bone has limited repeated sampling of tumor deposits. Hence, considerably less is understood about this lethal metastatic disease, as it is not commonly studied. Here we explored whole-genome sequencing of plasma DNA to scan the tumor genomes of these patients non-invasively. We wanted to make whole-genome analysis from plasma DNA amenable to clinical routine applications and developed an approach based on a benchtop high-throughput platform, that is, Illuminas MiSeq instrument. We performed whole-genome sequencing from plasma at a shallow sequencing depth to establish a genome-wide copy number profile of the tumor at low costs within 2 days. In parallel, we sequenced a panel of 55 high-interest genes and 38 introns with frequent fusion breakpoints such as the TMPRSS2-ERG fusion with high coverage. After intensive testing of our approach with samples from 25 individuals without cancer we analyzed 13 plasma samples derived from five patients with castration resistant (CRPC) and four patients with castration sensitive prostate cancer (CSPC). The genome-wide profiling in the plasma of our patients revealed multiple copy number aberrations including those previously reported in prostate tumors, such as losses in 8p and gains in 8q. High-level copy number gains in the AR locus were observed in patients with CRPC but not with CSPC disease. We identified the TMPRSS2-ERG rearrangement associated 3-Mbp deletion on chromosome 21 and found corresponding fusion plasma fragments in these cases. In an index case multiregional sequencing of the primary tumor identified different copy number changes in each sector, suggesting multifocal disease. Our plasma analyses of this index case, performed 13 years after resection of the primary tumor, revealed novel chromosomal rearrangements, which were stable in serial plasma analyses over a 9-month period, which is consistent with the presence of one metastatic clone. The genomic landscape of prostate cancer can be established by non-invasive means from plasma DNA. Our approach provides specific genomic signatures within 2 days which may therefore serve as 'liquid biopsy'.
      datePublished:2013-04-05T00:00:00Z
      dateModified:2013-04-05T00:00:00Z
      pageStart:1
      pageEnd:16
      license:http://creativecommons.org/licenses/by/2.0/
      sameAs:https://doi.org/10.1186/gm434
      keywords:
         Prostate Cancer
         Androgen Receptor
         Metastatic Prostate Cancer
         Copy Number Change
         Copy Number Aberration
         Human Genetics
         Metabolomics
         Bioinformatics
         Medicine/Public Health
         general
         Cancer Research
         Systems Biology
      image:
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1186%2Fgm434/MediaObjects/13073_2013_Article_439_Fig1_HTML.jpg
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         name:Genome Medicine
         issn:
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            PublicationVolume
      publisher:
         name:BioMed Central
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            type:ImageObject
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      author:
            name:Ellen Heitzer
            affiliation:
                  name:Institute of Human Genetics, Medical University of Graz
                  address:
                     name:Institute of Human Genetics, Medical University of Graz, Graz, Austria
                     type:PostalAddress
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            name:Peter Ulz
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                  name:Institute of Human Genetics, Medical University of Graz
                  address:
                     name:Institute of Human Genetics, Medical University of Graz, Graz, Austria
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Jelena Belic
            affiliation:
                  name:Institute of Human Genetics, Medical University of Graz
                  address:
                     name:Institute of Human Genetics, Medical University of Graz, Graz, Austria
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Stefan Gutschi
            affiliation:
                  name:Medical University of Graz
                  address:
                     name:Department of Urology, Medical University of Graz, Graz, Austria
                     type:PostalAddress
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            name:Franz Quehenberger
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                  name:Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz
                  address:
                     name:Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria
                     type:PostalAddress
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            name:Katja Fischereder
            affiliation:
                  name:Medical University of Graz
                  address:
                     name:Department of Urology, Medical University of Graz, Graz, Austria
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Theresa Benezeder
            affiliation:
                  name:Institute of Human Genetics, Medical University of Graz
                  address:
                     name:Institute of Human Genetics, Medical University of Graz, Graz, Austria
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Martina Auer
            affiliation:
                  name:Institute of Human Genetics, Medical University of Graz
                  address:
                     name:Institute of Human Genetics, Medical University of Graz, Graz, Austria
                     type:PostalAddress
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            name:Carina Pischler
            affiliation:
                  name:Institute of Human Genetics, Medical University of Graz
                  address:
                     name:Institute of Human Genetics, Medical University of Graz, Graz, Austria
                     type:PostalAddress
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            type:Person
            name:Sebastian Mannweiler
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                  name:Institute of Pathology, Medical University of Graz
                  address:
                     name:Institute of Pathology, Medical University of Graz, Graz, Austria
                     type:PostalAddress
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            name:Martin Pichler
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                  name:Medical University of Graz
                  address:
                     name:Division of Oncology, Medical University of Graz, Graz, Austria
                     type:PostalAddress
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            name:Florian Eisner
            affiliation:
                  name:Medical University of Graz
                  address:
                     name:Division of Oncology, Medical University of Graz, Graz, Austria
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Martin Haeusler
            affiliation:
                  name:Medical University of Graz
                  address:
                     name:Department of Obstetrics and Gynecology, Medical University of Graz, Graz, Austria
                     type:PostalAddress
                  type:Organization
            type:Person
            name:Sabine Riethdorf
            affiliation:
                  name:Institute of Tumor Biology, University Medical Center Hamburg Eppendorf
                  address:
                     name:Institute of Tumor Biology, University Medical Center Hamburg Eppendorf, Hamburg, Germany
                     type:PostalAddress
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            name:Klaus Pantel
            affiliation:
                  name:Institute of Tumor Biology, University Medical Center Hamburg Eppendorf
                  address:
                     name:Institute of Tumor Biology, University Medical Center Hamburg Eppendorf, Hamburg, Germany
                     type:PostalAddress
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            name:Hellmut Samonigg
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                  address:
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                  address:
                     name:Institute of Pathology, Medical University of Graz, Graz, Austria
                     type:PostalAddress
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            name:Herbert Augustin
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                  name:Medical University of Graz
                  address:
                     name:Department of Urology, Medical University of Graz, Graz, Austria
                     type:PostalAddress
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            name:Jochen B Geigl
            affiliation:
                  name:Institute of Human Genetics, Medical University of Graz
                  address:
                     name:Institute of Human Genetics, Medical University of Graz, Graz, Austria
                     type:PostalAddress
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            email:[email protected]
            type:Person
            name:Michael R Speicher
            affiliation:
                  name:Institute of Human Genetics, Medical University of Graz
                  address:
                     name:Institute of Human Genetics, Medical University of Graz, Graz, Austria
                     type:PostalAddress
                  type:Organization
            email:[email protected]
            type:Person
      isAccessibleForFree:1
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      address:
         name:Institute of Human Genetics, Medical University of Graz, Graz, Austria
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      name:Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria
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