Mutational Landscapes of Sequential Prostate Metastases and Matched Patient Derived Xenografts during Enzalutamide Therapy
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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2614784", "https://ndownloader.figshare.com/files/2614790", "https://ndownloader.figshare.com/files/2614796", "https://ndownloader.figshare.com/files/2614797", "https://ndownloader.figshare.com/files/2614798", "https://ndownloader.figshare.com/files/2614799", "https://ndownloader.figshare.com/files/2614800", "https://ndownloader.figshare.com/files/2614801", "https://ndownloader.figshare.com/files/2614802", "https://ndownloader.figshare.com/files/2614803", "https://ndownloader.figshare.com/files/2614804", "https://ndownloader.figshare.com/files/2614805", "https://ndownloader.figshare.com/files/2614806", "https://ndownloader.figshare.com/files/2614807", "https://ndownloader.figshare.com/files/2614808", "https://ndownloader.figshare.com/files/2614809", "https://ndownloader.figshare.com/files/2614810"], "description"=>"<div><p>Developing patient derived models from individual tumors that capture the biological heterogeneity and mutation landscape in advanced prostate cancer is challenging, but essential for understanding tumor progression and delivery of personalized therapy in metastatic castrate resistant prostate cancer stage. To demonstrate the feasibility of developing patient derived xenograft models in this stage, we present a case study wherein xenografts were derived from cancer metastases in a patient progressing on androgen deprivation therapy and prior to initiating pre-chemotherapy enzalutamide treatment. Tissue biopsies from a metastatic rib lesion were obtained for sequencing before and after initiating enzalutamide treatment over a twelve-week period and also implanted subcutaneously as well as under the renal capsule in immuno-deficient mice. The genome and transcriptome landscapes of xenografts and the original patient tumor tissues were compared by performing whole exome and transcriptome sequencing of the metastatic tumor tissues and the xenografts at both time points. After comparing the somatic mutations, copy number variations, gene fusions and gene expression we found that the patient’s genomic and transcriptomic alterations were preserved in the patient derived xenografts with high fidelity. These xenograft models provide an opportunity for predicting efficacy of existing and potentially novel drugs that is based on individual metastatic tumor expression signature and molecular pharmacology for delivery of precision medicine.</p></div>", "links"=>[], "tags"=>["Sequential Prostate Metastases", "patient tumor tissues", "prostate cancer stage", "copy number variations", "androgen deprivation therapy", "Matched Patient Derived Xenografts", "metastatic rib lesion", "metastatic tumor expression signature", "xenograft models", "understanding tumor progression", "metastatic tumor tissues"], "article_id"=>1628968, "categories"=>["Biological Sciences"], "users"=>["Manish Kohli", "Liguo Wang", "Fang Xie", "Hugues Sicotte", "Ping Yin", "Scott M. Dehm", "Steven N. Hart", "Peter T. Vedell", "Poulami Barman", "Rui Qin", "Douglas W. Mahoney", "Rachel E. Carlson", "Jeanette E. Eckel-Passow", "Thomas D. Atwell", "Patrick W. Eiken", "Brendan P. McMenomy", "Eric D. Wieben", "Gautam Jha", "Rafael E. Jimenez", "Richard Weinshilboum", "Liewei Wang"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0145176.s001", "https://dx.doi.org/10.1371/journal.pone.0145176.s002", "https://dx.doi.org/10.1371/journal.pone.0145176.s003", "https://dx.doi.org/10.1371/journal.pone.0145176.s004", "https://dx.doi.org/10.1371/journal.pone.0145176.s005", "https://dx.doi.org/10.1371/journal.pone.0145176.s006", "https://dx.doi.org/10.1371/journal.pone.0145176.s007", "https://dx.doi.org/10.1371/journal.pone.0145176.s008", "https://dx.doi.org/10.1371/journal.pone.0145176.s009", "https://dx.doi.org/10.1371/journal.pone.0145176.s010", "https://dx.doi.org/10.1371/journal.pone.0145176.s011", "https://dx.doi.org/10.1371/journal.pone.0145176.s012", "https://dx.doi.org/10.1371/journal.pone.0145176.s013", "https://dx.doi.org/10.1371/journal.pone.0145176.s014", "https://dx.doi.org/10.1371/journal.pone.0145176.s015", "https://dx.doi.org/10.1371/journal.pone.0145176.s016", "https://dx.doi.org/10.1371/journal.pone.0145176.s017"], "stats"=>{"downloads"=>15, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mutational_Landscapes_of_Sequential_Prostate_Metastases_and_Matched_Patient_Derived_Xenografts_during_Enzalutamide_Therapy_/1628968", "title"=>"Mutational Landscapes of Sequential Prostate Metastases and Matched Patient Derived Xenografts during Enzalutamide Therapy", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2016-01-05 14:52:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/2614768"], "description"=>"<p>Reads generated from xenograft samples were divided into five groups including “graft”, “host”, “both”, “neither” and “ambiguous” using tool developed by Conway et al. (A) Reads assignments for 10 xenograft whole exome sequencing data. (B) Average proportion of whole exome sequencing reads assigned to the 5 groups mentioned above. (C) Reads assignments for 10 xenograft RNA-seq data. (D) Average proportion of RNA-seq reads assigned to the 5 groups mentioned above.</p>", "links"=>[], "tags"=>["Sequential Prostate Metastases", "patient tumor tissues", "prostate cancer stage", "copy number variations", "androgen deprivation therapy", "Matched Patient Derived Xenografts", "metastatic rib lesion", "metastatic tumor expression signature", "xenograft models", "understanding tumor progression", "metastatic tumor tissues"], "article_id"=>1628953, "categories"=>["Biological Sciences"], "users"=>["Manish Kohli", "Liguo Wang", "Fang Xie", "Hugues Sicotte", "Ping Yin", "Scott M. Dehm", "Steven N. Hart", "Peter T. Vedell", "Poulami Barman", "Rui Qin", "Douglas W. Mahoney", "Rachel E. Carlson", "Jeanette E. Eckel-Passow", "Thomas D. Atwell", "Patrick W. Eiken", "Brendan P. McMenomy", "Eric D. Wieben", "Gautam Jha", "Rafael E. Jimenez", "Richard Weinshilboum", "Liewei Wang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0145176.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Classification_of_xenograft_whole_exome_sequencing_panels_A_and_B_and_RNA_sequencing_reads_panels_C_and_D_/1628953", "title"=>"Classification of xenograft whole exome sequencing (panels A and B) and RNA sequencing reads (panels C and D).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-01-06 09:32:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/2614770"], "description"=>"<p>(A) Recall (grey) and precision (tan) of detected somatic mutations. Recall = number of somatic mutations called from both patient tissue and xenograft divided by total somatic mutations called from patient tissue; Precision = number of somatic mutations called from both patient tissue and xenograft divided by total mutations called from xenograft. (B) Heatmap showing the concordance of relative allele frequency of somatic mutations between patient tissues and xenografts. Rows correspond to patients and xenograft samples and columns correspond to 60 selected somatic mutations. (C) Circos plot showing profiles of copy number variation for patient tumor tissues and xenografts. From outside to inside, tracks correspond to 1 = V1/met, 1A = V1/xeno/A, 1B = V1/xeno/B, 1C = V1/xeno/C, 1AA = V1/xeno/A/A, 1BA = V1/xeno/B/A, V1/xeno/C/A, V2/met, V2/xeno/A, V2/xeno/A/A1, V2/xeno/A/A2 and V2/xeno/A/B. (D) Pair-wise gene expression correlation between patient tissues and xenografts. Correlation was measured by Pearson correlation coefficient. Gene expression was measured by log10 (RPKM, Reads Per Kilobase exon per Million mapped reads).</p>", "links"=>[], "tags"=>["Sequential Prostate Metastases", "patient tumor tissues", "prostate cancer stage", "copy number variations", "androgen deprivation therapy", "Matched Patient Derived Xenografts", "metastatic rib lesion", "metastatic tumor expression signature", "xenograft models", "understanding tumor progression", "metastatic tumor tissues"], "article_id"=>1628955, "categories"=>["Biological Sciences"], "users"=>["Manish Kohli", "Liguo Wang", "Fang Xie", "Hugues Sicotte", "Ping Yin", "Scott M. Dehm", "Steven N. Hart", "Peter T. Vedell", "Poulami Barman", "Rui Qin", "Douglas W. Mahoney", "Rachel E. Carlson", "Jeanette E. Eckel-Passow", "Thomas D. Atwell", "Patrick W. Eiken", "Brendan P. McMenomy", "Eric D. Wieben", "Gautam Jha", "Rafael E. Jimenez", "Richard Weinshilboum", "Liewei Wang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0145176.g002", "stats"=>{"downloads"=>3, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_genome_and_transcriptome_landscapes_between_patient_tumor_tissue_and_patient_derived_xenograft_models_PDXs_/1628955", "title"=>"Comparison of genome and transcriptome landscapes between patient tumor tissue and patient derived xenograft models (PDXs).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-01-05 14:52:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/2614771"], "description"=>"<p>The upper gel images showed the targeted amplification products, and the lower gel images showed the loading control amplification (GAPDH). (A) The amplification products for PNPO-TMPRSS2 fusion was detected in the xenograft sample V1/xeon/C/A. (B) TRIP4-TMPRSS2 fusion was detected in V2/xeno/A/A1. (C) Three different types of TMRPSS2-ETV4 fusions were detected in V2/Xeno/A. The sample V1/Xeno/A1 was used as negative control.</p>", "links"=>[], "tags"=>["Sequential Prostate Metastases", "patient tumor tissues", "prostate cancer stage", "copy number variations", "androgen deprivation therapy", "Matched Patient Derived Xenografts", "metastatic rib lesion", "metastatic tumor expression signature", "xenograft models", "understanding tumor progression", "metastatic tumor tissues"], "article_id"=>1628956, "categories"=>["Biological Sciences"], "users"=>["Manish Kohli", "Liguo Wang", "Fang Xie", "Hugues Sicotte", "Ping Yin", "Scott M. Dehm", "Steven N. Hart", "Peter T. Vedell", "Poulami Barman", "Rui Qin", "Douglas W. Mahoney", "Rachel E. Carlson", "Jeanette E. Eckel-Passow", "Thomas D. Atwell", "Patrick W. Eiken", "Brendan P. McMenomy", "Eric D. Wieben", "Gautam Jha", "Rafael E. Jimenez", "Richard Weinshilboum", "Liewei Wang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0145176.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Validation_of_gene_fusion_products_identified_by_RNA_seq_/1628956", "title"=>"Validation of gene fusion products identified by RNA seq.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-01-05 14:52:40"}

PMC Usage Stats | Further Information

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Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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