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xenografts, tumor, tumors, analysis, xenograft, gene, cancer, expression, breast, patient, primary, human, article, genomic, pairs, figure, profiles, pubmed, molecular, table, google, scholar, genes, probe, data, number, performed, showed, profile, differences, sets, dna, cna, correlation, regions, observed, hbc, patients, chromosomal, france, hbcx, cas, copy, gains, original, models, alterations, loss, array, cell,

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fr/publications/recherche_translationnelle/characterization_of_xenografts/files/affymetrixdata metastasis-derived xenografts hbcx-13b editing assistance post-submission article download pdf hematoxylin-eosin-saffron stained sections saint-quentin-en-yvelines hbcx-13a/13b pairs clustered full size image p1-derived artificial chromosome worldwide cancer-related death examining paraffin-embedded sections translational research department axillary metastasis-derived xenograft gene expression profiling anne vincent-salomon breast tumor-derived xenograft pathogen-free animal housing full access linear regression model breast cancer metastasis linear regression models patricia de cremoux related subjects primary tumor-derived xenograft primary tumor-derived xenografts human breast cancer triple-negative tumor hbc article number r11 breast cancer pathophysiologies natl cancer inst privacy choices/manage cookies gene expression values gene expression stability metastasis-derived xenograft cancer research immune response-related genes primary hbc-12b tumor metastasis-derived xenografts gene expression analysis gene expression profile hierarchical clustering analysis breast cancer xenografts human breast tumours gene expression differences cancer genet cytogenet axillary lymph node relative log expression gene ontology analysis patient-derived models gene copy numbers

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         headline:Molecular profiling of patient-derived breast cancer xenografts
         description:Identification of new therapeutic agents for breast cancer (BC) requires preclinical models that reproduce the molecular characteristics of their respective clinical tumors. In this work, we analyzed the genomic and gene expression profiles of human BC xenografts and the corresponding patient tumors. Eighteen BC xenografts were obtained by grafting tumor fragments from patients into Swiss nude mice. Molecular characterization of patient tumors and xenografts was performed by DNA copy number analysis and gene expression analysis using Affymetrix Microarrays. Comparison analysis showed that 14/18 pairs of tumors shared more than 56% of copy number alterations (CNA). Unsupervised hierarchical clustering analysis showed that 16/18 pairs segregated together, confirming the similarity between tumor pairs. Analysis of recurrent CNA changes between patient tumors and xenografts showed losses in 176 chromosomal regions and gains in 202 chromosomal regions. Gene expression profile analysis showed that less than 5% of genes had recurrent variations between patient tumors and their respective xenografts; these genes largely corresponded to human stromal compartment genes. Finally, analysis of different passages of the same tumor showed that sequential mouse-to-mouse tumor grafts did not affect genomic rearrangements or gene expression profiles, suggesting genetic stability of these models over time. This panel of human BC xenografts maintains the overall genomic and gene expression profile of the corresponding patient tumors and remains stable throughout sequential in vivo generations. The observed genomic profile and gene expression differences appear to be due to the loss of human stromal genes. These xenografts, therefore, represent a validated model for preclinical investigation of new therapeutic agents.
         datePublished:2012-01-16T00:00:00Z
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            xenograft
            genomic and expression profiles
            Cancer Research
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            Surgical Oncology
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      headline:Molecular profiling of patient-derived breast cancer xenografts
      description:Identification of new therapeutic agents for breast cancer (BC) requires preclinical models that reproduce the molecular characteristics of their respective clinical tumors. In this work, we analyzed the genomic and gene expression profiles of human BC xenografts and the corresponding patient tumors. Eighteen BC xenografts were obtained by grafting tumor fragments from patients into Swiss nude mice. Molecular characterization of patient tumors and xenografts was performed by DNA copy number analysis and gene expression analysis using Affymetrix Microarrays. Comparison analysis showed that 14/18 pairs of tumors shared more than 56% of copy number alterations (CNA). Unsupervised hierarchical clustering analysis showed that 16/18 pairs segregated together, confirming the similarity between tumor pairs. Analysis of recurrent CNA changes between patient tumors and xenografts showed losses in 176 chromosomal regions and gains in 202 chromosomal regions. Gene expression profile analysis showed that less than 5% of genes had recurrent variations between patient tumors and their respective xenografts; these genes largely corresponded to human stromal compartment genes. Finally, analysis of different passages of the same tumor showed that sequential mouse-to-mouse tumor grafts did not affect genomic rearrangements or gene expression profiles, suggesting genetic stability of these models over time. This panel of human BC xenografts maintains the overall genomic and gene expression profile of the corresponding patient tumors and remains stable throughout sequential in vivo generations. The observed genomic profile and gene expression differences appear to be due to the loss of human stromal genes. These xenografts, therefore, represent a validated model for preclinical investigation of new therapeutic agents.
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      dateModified:2012-01-16T00:00:00Z
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         Oncology
         Surgical Oncology
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            type:Organization
      name:Ludmilla De Plater
      affiliation:
            name:Institut Curie
            address:
               name:Translational Research Department, Institut Curie, Paris, France
               type:PostalAddress
            type:Organization
      name:David Gentien
      affiliation:
            name:Institut Curie
            address:
               name:Affymetrix platform, Translational Research Department, Institut Curie, Paris, France
               type:PostalAddress
            type:Organization
      name:Marie-France Poupon
      affiliation:
            name:Institut Curie
            address:
               name:Translational Research Department, Institut Curie, Paris, France
               type:PostalAddress
            type:Organization
      name:Paul Cottu
      affiliation:
            name:Institut Curie
            address:
               name:Translational Research Department, Institut Curie, Paris, France
               type:PostalAddress
            type:Organization
            name:Institut Curie
            address:
               name:Department of Medical Oncology, Institut Curie, Paris, France
               type:PostalAddress
            type:Organization
      name:Patricia De Cremoux
      affiliation:
            name:Institut Curie
            address:
               name:Department of Tumor Biology, Institut Curie, Paris, France
               type:PostalAddress
            type:Organization
      name:Pierre Gestraud
      affiliation:
            name:Bioinformatics, Institut Curie
            address:
               name:Bioinformatics, Institut Curie, Paris, France
               type:PostalAddress
            type:Organization
      name:Anne Vincent-Salomon
      affiliation:
            name:Institut Curie
            address:
               name:Department of Tumor Biology, Institut Curie, Paris, France
               type:PostalAddress
            type:Organization
      name:Jean-Jacques Fontaine
      affiliation:
            name:National Veterinary School of Alfort
            address:
               name:National Veterinary School of Alfort, Maisons Alfort, France
               type:PostalAddress
            type:Organization
      name:Sergio Roman-Roman
      affiliation:
            name:Institut Curie
            address:
               name:Translational Research Department, Institut Curie, Paris, France
               type:PostalAddress
            type:Organization
      name:Olivier Delattre
      affiliation:
            name:INSERM U830, Institut Curie
            address:
               name:INSERM U830, Institut Curie, Paris, France
               type:PostalAddress
            type:Organization
      name:Didier Decaudin
      affiliation:
            name:Institut Curie
            address:
               name:Translational Research Department, Institut Curie, Paris, France
               type:PostalAddress
            type:Organization
            name:Institut Curie
            address:
               name:Department of Medical Oncology, Institut Curie, Paris, France
               type:PostalAddress
            type:Organization
      name:Elisabetta Marangoni
      affiliation:
            name:Institut Curie
            address:
               name:Translational Research Department, Institut Curie, Paris, France
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Surgery and UMR144 Institut Curie, Molecular Oncology Team, Institut Curie, Paris, France
      name:Translational Research Department, Institut Curie, Paris, France
      name:Translational Research Department, Institut Curie, Paris, France
      name:CNRS, UMR144, Institut Curie, Paris, France
      name:INSERM U830, Institut Curie, Paris, France
      name:Translational Research Department, Institut Curie, Paris, France
      name:Translational Research Department, Institut Curie, Paris, France
      name:Translational Research Department, Institut Curie, Paris, France
      name:Affymetrix platform, Translational Research Department, Institut Curie, Paris, France
      name:Translational Research Department, Institut Curie, Paris, France
      name:Translational Research Department, Institut Curie, Paris, France
      name:Department of Medical Oncology, Institut Curie, Paris, France
      name:Department of Tumor Biology, Institut Curie, Paris, France
      name:Bioinformatics, Institut Curie, Paris, France
      name:Department of Tumor Biology, Institut Curie, Paris, France
      name:National Veterinary School of Alfort, Maisons Alfort, France
      name:Translational Research Department, Institut Curie, Paris, France
      name:INSERM U830, Institut Curie, Paris, France
      name:Translational Research Department, Institut Curie, Paris, France
      name:Department of Medical Oncology, Institut Curie, Paris, France
      name:Translational Research Department, Institut Curie, Paris, France

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