A Melanoma Brain Metastasis with a Donor-Patient Hybrid Genome following Bone Marrow Transplantation: First Evidence for Fusion in Human Cancer
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{"title"=>"A Melanoma Brain Metastasis with a Donor-Patient Hybrid Genome following Bone Marrow Transplantation: First Evidence for Fusion in Human Cancer", "type"=>"journal", "authors"=>[{"first_name"=>"Rossitza", "last_name"=>"Lazova", "scopus_author_id"=>"6602905363"}, {"first_name"=>"Greggory S.", "last_name"=>"LaBerge", "scopus_author_id"=>"6603430214"}, {"first_name"=>"Eric", "last_name"=>"Duvall", "scopus_author_id"=>"24499241800"}, {"first_name"=>"Nicole", "last_name"=>"Spoelstra", "scopus_author_id"=>"6507368528"}, {"first_name"=>"Vincent", "last_name"=>"Klump", "scopus_author_id"=>"6505782736"}, {"first_name"=>"Mario", "last_name"=>"Sznol", "scopus_author_id"=>"7007173539"}, {"first_name"=>"Dennis", "last_name"=>"Cooper", "scopus_author_id"=>"56295909600"}, {"first_name"=>"Richard A.", "last_name"=>"Spritz", "scopus_author_id"=>"7006548083"}, {"first_name"=>"Joseph T.", "last_name"=>"Chang", "scopus_author_id"=>"57141165900"}, {"first_name"=>"John M.", "last_name"=>"Pawelek", "scopus_author_id"=>"7005960064"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84879469812", "issn"=>"19326203", "scopus"=>"2-s2.0-84879469812", "pmid"=>"23840523", "pui"=>"369200449", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "doi"=>"10.1371/journal.pone.0066731"}, "id"=>"51828cb5-f431-3663-aa75-9363667f2c79", "abstract"=>"BACKGROUND: Tumor cell fusion with motile bone marrow-derived cells (BMDCs) has long been posited as a mechanism for cancer metastasis. While there is much support for this from cell culture and animal studies, it has yet to be confirmed in human cancer, as tumor and marrow-derived cells from the same patient cannot be easily distinguished genetically. METHODS: We carried out genotyping of a metastatic melanoma to the brain that arose following allogeneic bone-marrow transplantation (BMT), using forensic short tandem repeat (STR) length-polymorphisms to distinguish donor and patient genomes. Tumor cells were isolated free of leucocytes by laser microdissection, and tumor and pre-transplant blood lymphocyte DNAs were analyzed for donor and patient alleles at 14 autosomal STR loci and the sex chromosomes. RESULTS: All alleles in the donor and patient pre-BMT lymphocytes were found in tumor cells. The alleles showed disproportionate relative abundances in similar patterns throughout the tumor, indicating the tumor was initiated by a clonal fusion event. CONCLUSIONS: Our results strongly support fusion between a BMDC and a tumor cell playing a role in the origin of this metastasis. Depending on the frequency of such events, the findings could have important implications for understanding the generation of metastases, including the origins of tumor initiating cells and the cancer epigenome.", "link"=>"http://www.mendeley.com/research/melanoma-brain-metastasis-donorpatient-hybrid-genome-following-bone-marrow-transplantation-first-evi", "reader_count"=>45, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>9, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>12, "Student > Postgraduate"=>3, "Other"=>1, "Student > Master"=>2, "Student > Bachelor"=>6, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>9, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>12, "Student > Postgraduate"=>3, "Other"=>1, "Student > Master"=>2, "Student > Bachelor"=>6, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>3, "Materials Science"=>1, "Agricultural and Biological Sciences"=>20, "Medicine and Dentistry"=>12, "Neuroscience"=>1, "Physics and Astronomy"=>1, "Chemistry"=>1, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Materials Science"=>{"Materials Science"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>12}, "Neuroscience"=>{"Neuroscience"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>20}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>3}}, "reader_count_by_country"=>{"United States"=>1, "Japan"=>1, "South Africa"=>1, "India"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1101989"], "description"=>"<p>A. An area with brown LCA/CD45-positive leucocytes (arrow) intermixed with blue LCA/CD45-negative cancer cells. B-D. Adjacent areas from the same section containing only blue LCA/CD45-negative cancer cells.</p>", "links"=>[], "tags"=>["Evolutionary biology", "Evolutionary processes", "hybridization", "genetics", "genomics", "immunology", "Immune cells", "monocytes", "Immune response", "Molecular cell biology", "Cellular types", "stem cells", "Hematopoietic stem cells", "Blood cells", "Bone marrow cells", "Hematopoietic progenitor cells", "dermatology", "Skin neoplasms", "Malignant skin neoplasms", "melanomas", "Dermatologic pathology", "Pigmentary disorders", "oncology", "Basic cancer research", "metastasis", "Cancers and neoplasms", "Neurological tumors", "Brain metastasis", "Skin tumors", "Malignant melanoma", "mh3", "melanoma", "stained", "counterstained", "hematoxylin"], "article_id"=>732227, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Rossitza Lazova", "Greggory S. LaBerge", "Eric Duvall", "Nicole Spoelstra", "Vincent Klump", "Mario Sznol", "Dennis Cooper", "Richard A. Spritz", "Joseph T. Chang", "John M. Pawelek"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0066731.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_section_of_the_MH3_melanoma_brain_metastasis_stained_for_LCA_CD45_brown_chromogen_and_counterstained_with_hematoxylin_blue_/732227", "title"=>"A section of the MH3 melanoma brain metastasis stained for LCA/CD45 (brown chromogen) and counterstained with hematoxylin (blue).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-26 08:53:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/1101991"], "description"=>"<p>A. An area of S100-positive tumor cells admixed with infiltrating S100-negative leucocytes (arrows). B. An area containing only S100-positive tumor cells. More detailed pathology analyses are presented in Figs S3 and S4 in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0066731#pone.0066731.s001\" target=\"_blank\">File S1</a>.</p>", "links"=>[], "tags"=>["Evolutionary biology", "Evolutionary processes", "hybridization", "genetics", "genomics", "immunology", "Immune cells", "monocytes", "Immune response", "Molecular cell biology", "Cellular types", "stem cells", "Hematopoietic stem cells", "Blood cells", "Bone marrow cells", "Hematopoietic progenitor cells", "dermatology", "Skin neoplasms", "Malignant skin neoplasms", "melanomas", "Dermatologic pathology", "Pigmentary disorders", "oncology", "Basic cancer research", "metastasis", "Cancers and neoplasms", "Neurological tumors", "Brain metastasis", "Skin tumors", "Malignant melanoma", "adjacent", "stained", "melanoma-specific", "antigen"], "article_id"=>732228, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Rossitza Lazova", "Greggory S. LaBerge", "Eric Duvall", "Nicole Spoelstra", "Vincent Klump", "Mario Sznol", "Dennis Cooper", "Richard A. Spritz", "Joseph T. Chang", "John M. Pawelek"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0066731.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_An_adjacent_section_to_that_in_Fig_1_stained_for_the_melanoma_specific_antigen_S100_/732228", "title"=>"An adjacent section to that in Fig. 1 stained for the melanoma-specific antigen S100.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-26 08:53:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/1101992"], "description"=>"<p>Shown are “informative” loci exhibiting donor and patient specific alleles in pre-BMT lymphocytes. Tumor loci are listed in order of relative abundance of the donor-specific alleles (red asterisk) compared to patient-specific (blue asterisk) and shared alleles (black asterisk). Allele peaks <50 relative fluorescence units were censored as “no call” (open circles). Loci with no detectable alleles after PCR amplification (—).</p>", "links"=>[], "tags"=>["Evolutionary biology", "Evolutionary processes", "hybridization", "genetics", "genomics", "immunology", "Immune cells", "monocytes", "Immune response", "Molecular cell biology", "Cellular types", "stem cells", "Hematopoietic stem cells", "Blood cells", "Bone marrow cells", "Hematopoietic progenitor cells", "dermatology", "Skin neoplasms", "Malignant skin neoplasms", "melanomas", "Dermatologic pathology", "Pigmentary disorders", "oncology", "Basic cancer research", "metastasis", "Cancers and neoplasms", "Neurological tumors", "Brain metastasis", "Skin tumors", "Malignant melanoma", "str", "mh3", "melanoma", "pre-bmt"], "article_id"=>732229, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Rossitza Lazova", "Greggory S. LaBerge", "Eric Duvall", "Nicole Spoelstra", "Vincent Klump", "Mario Sznol", "Dennis Cooper", "Richard A. Spritz", "Joseph T. Chang", "John M. Pawelek"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0066731.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Forensic_STR_analyses_of_the_MH3_melanoma_along_with_donor_and_patient_pre_BMT_lymphocytes_/732229", "title"=>"Forensic STR analyses of the MH3 melanoma along with donor and patient pre-BMT lymphocytes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-26 08:53:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/1101993"], "description"=>"<p>Panels A and B: Deviances under contamination and fusion models; smaller deviances indicate better fit. Panels C and D: A calibration procedure shows the observed LPML difference (red lines) is rare under the contamination model but typical under the fusion model. More detailed statistical analyses are presented in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0066731#pone.0066731.s002\" target=\"_blank\">File S2</a>.</p>", "links"=>[], "tags"=>["Evolutionary biology", "Evolutionary processes", "hybridization", "genetics", "genomics", "immunology", "Immune cells", "monocytes", "Immune response", "Molecular cell biology", "Cellular types", "stem cells", "Hematopoietic stem cells", "Blood cells", "Bone marrow cells", "Hematopoietic progenitor cells", "dermatology", "Skin neoplasms", "Malignant skin neoplasms", "melanomas", "Dermatologic pathology", "Pigmentary disorders", "oncology", "Basic cancer research", "metastasis", "Cancers and neoplasms", "Neurological tumors", "Brain metastasis", "Skin tumors", "Malignant melanoma", "comparisons", "markov", "monte", "carlo", "allelic"], "article_id"=>732230, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Rossitza Lazova", "Greggory S. LaBerge", "Eric Duvall", "Nicole Spoelstra", "Vincent Klump", "Mario Sznol", "Dennis Cooper", "Richard A. Spritz", "Joseph T. Chang", "John M. Pawelek"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0066731.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Model_comparisons_using_Markov_chain_Monte_Carlo_analyses_of_allelic_data_/732230", "title"=>"Model comparisons using Markov chain Monte Carlo analyses of allelic data.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-26 08:53:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/1101995"], "description"=>"<p>A motile BMDC (red) such as a macrophage or stem cell is drawn to a cancer cell (blue). The outer cell membranes of the two cells become attached. Fusion occurs with the formation of a bi-nucleated heterokaryon having a nucleus from each of the fusion partners. The heterokaryon goes through genomic hybridization creating a melanoma-BMDC hybrid with co-expressed epigenomes, conferring deregulated cell division and metastatic competence to the hybrid.</p>", "links"=>[], "tags"=>["Evolutionary biology", "Evolutionary processes", "hybridization", "genetics", "genomics", "immunology", "Immune cells", "monocytes", "Immune response", "Molecular cell biology", "Cellular types", "stem cells", "Hematopoietic stem cells", "Blood cells", "Bone marrow cells", "Hematopoietic progenitor cells", "dermatology", "Skin neoplasms", "Malignant skin neoplasms", "melanomas", "Dermatologic pathology", "Pigmentary disorders", "oncology", "Basic cancer research", "metastasis", "Cancers and neoplasms", "Neurological tumors", "Brain metastasis", "Skin tumors", "Malignant melanoma", "bmdc-cancer", "fusion"], "article_id"=>732232, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Rossitza Lazova", "Greggory S. LaBerge", "Eric Duvall", "Nicole Spoelstra", "Vincent Klump", "Mario Sznol", "Dennis Cooper", "Richard A. Spritz", "Joseph T. Chang", "John M. Pawelek"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0066731.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_BMDC_cancer_cell_fusion_hypothesis_/732232", "title"=>"The BMDC-cancer cell fusion hypothesis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-26 08:53:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/1101996"], "description"=>"*<p>STR units: number of tandem repeats of the locus-specific tetranucleotide sequence. The X and Y chromosomes were detected by the amelogenin assay <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0066731#pone.0066731-Collins1\" target=\"_blank\">[25]</a>.</p>", "links"=>[], "tags"=>["Evolutionary biology", "Evolutionary processes", "hybridization", "genetics", "genomics", "immunology", "Immune cells", "monocytes", "Immune response", "Molecular cell biology", "Cellular types", "stem cells", "Hematopoietic stem cells", "Blood cells", "Bone marrow cells", "Hematopoietic progenitor cells", "dermatology", "Skin neoplasms", "Malignant skin neoplasms", "melanomas", "Dermatologic pathology", "Pigmentary disorders", "oncology", "Basic cancer research", "metastasis", "Cancers and neoplasms", "Neurological tumors", "Brain metastasis", "Skin tumors", "Malignant melanoma", "loci", "patient-specific"], "article_id"=>732233, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Rossitza Lazova", "Greggory S. LaBerge", "Eric Duvall", "Nicole Spoelstra", "Vincent Klump", "Mario Sznol", "Dennis Cooper", "Richard A. Spritz", "Joseph T. Chang", "John M. Pawelek"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0066731.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_STR_loci_with_donor_D_patient_specific_P_and_shared_S_alleles_/732233", "title"=>"STR loci with donor (D), patient-specific (P) and shared (S) alleles.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-26 08:53:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/1101997"], "description"=>"*<p>STR units: number of tandem repeats of the locus-specific tetranucleotide sequence. The X and Y chromosomes were detected by the amelogenin assay <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0066731#pone.0066731-Collins1\" target=\"_blank\">[25]</a>.</p>", "links"=>[], "tags"=>["Evolutionary biology", "Evolutionary processes", "hybridization", "genetics", "genomics", "immunology", "Immune cells", "monocytes", "Immune response", "Molecular cell biology", "Cellular types", "stem cells", "Hematopoietic stem cells", "Blood cells", "Bone marrow cells", "Hematopoietic progenitor cells", "dermatology", "Skin neoplasms", "Malignant skin neoplasms", "melanomas", "Dermatologic pathology", "Pigmentary disorders", "oncology", "Basic cancer research", "metastasis", "Cancers and neoplasms", "Neurological tumors", "Brain metastasis", "Skin tumors", "Malignant melanoma", "loci", "patient-specific"], "article_id"=>732234, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Rossitza Lazova", "Greggory S. LaBerge", "Eric Duvall", "Nicole Spoelstra", "Vincent Klump", "Mario Sznol", "Dennis Cooper", "Richard A. Spritz", "Joseph T. Chang", "John M. Pawelek"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0066731.t002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_STR_loci_with_only_patient_specific_P_and_shared_alleles_/732234", "title"=>"STR loci with only patient-specific (P) and shared alleles.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-26 08:53:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/1102000", "https://ndownloader.figshare.com/files/1102001"], "description"=>"<div><p>Background</p><p>Tumor cell fusion with motile bone marrow-derived cells (BMDCs) has long been posited as a mechanism for cancer metastasis. While there is much support for this from cell culture and animal studies, it has yet to be confirmed in human cancer, as tumor and marrow-derived cells from the same patient cannot be easily distinguished genetically.</p><p>Methods</p><p>We carried out genotyping of a metastatic melanoma to the brain that arose following allogeneic bone-marrow transplantation (BMT), using forensic short tandem repeat (STR) length-polymorphisms to distinguish donor and patient genomes. Tumor cells were isolated free of leucocytes by laser microdissection, and tumor and pre-transplant blood lymphocyte DNAs were analyzed for donor and patient alleles at 14 autosomal STR loci and the sex chromosomes.</p><p>Results</p><p>All alleles in the donor and patient pre-BMT lymphocytes were found in tumor cells. The alleles showed disproportionate relative abundances in similar patterns throughout the tumor, indicating the tumor was initiated by a clonal fusion event.</p><p>Conclusions</p><p>Our results strongly support fusion between a BMDC and a tumor cell playing a role in the origin of this metastasis. Depending on the frequency of such events, the findings could have important implications for understanding the generation of metastases, including the origins of tumor initiating cells and the cancer epigenome.</p></div>", "links"=>[], "tags"=>["Evolutionary biology", "Evolutionary processes", "hybridization", "genetics", "genomics", "immunology", "Immune cells", "monocytes", "Immune response", "Molecular cell biology", "Cellular types", "stem cells", "Hematopoietic stem cells", "Blood cells", "Bone marrow cells", "Hematopoietic progenitor cells", "dermatology", "Skin neoplasms", "Malignant skin neoplasms", "melanomas", "Dermatologic pathology", "Pigmentary disorders", "oncology", "Basic cancer research", "metastasis", "Cancers and neoplasms", "Neurological tumors", "Brain metastasis", "Skin tumors", "Malignant melanoma", "melanoma", "donor-patient", "hybrid", "genome", "marrow", "fusion"], "article_id"=>732237, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Rossitza Lazova", "Greggory S. LaBerge", "Eric Duvall", "Nicole Spoelstra", "Vincent Klump", "Mario Sznol", "Dennis Cooper", "Richard A. Spritz", "Joseph T. Chang", "John M. Pawelek"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0066731.s001", "https://dx.doi.org/10.1371/journal.pone.0066731.s002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_Melanoma_Brain_Metastasis_with_a_Donor_Patient_Hybrid_Genome_following_Bone_Marrow_Transplantation_First_Evidence_for_Fusion_in_Human_Cancer_/732237", "title"=>"A Melanoma Brain Metastasis with a Donor-Patient Hybrid Genome following Bone Marrow Transplantation: First Evidence for Fusion in Human Cancer", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-06-26 08:53:02"}

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Relative Metric

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