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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Genomic profiling reveals extensive heterogeneity in somatic DNA copy number aberrations of canine hemangiosarcoma</title><author><name sortKey="Thomas, Rachael" sort="Thomas, Rachael" uniqKey="Thomas R" first="Rachael" last="Thomas">Rachael Thomas</name><affiliation><nlm:aff id="A1">Department of Molecular Biomedical Sciences, North Carolina State University College of Veterinary Medicine; Raleigh, NC, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, NC, USA</nlm:aff></affiliation></author><author><name sortKey="Borst, Luke" sort="Borst, Luke" uniqKey="Borst L" first="Luke" last="Borst">Luke Borst</name><affiliation><nlm:aff id="A2">Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, NC, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Department of Population Health and Pathobiology, North Carolina State University College of Veterinary Medicine, Raleigh, NC, USA</nlm:aff></affiliation></author><author><name sortKey="Rotroff, Daniel" sort="Rotroff, Daniel" uniqKey="Rotroff D" first="Daniel" last="Rotroff">Daniel Rotroff</name><affiliation><nlm:aff id="A4">Bioinformatics Research Center, Department of Statistics, North Carolina State University, Raleigh, NC, USA</nlm:aff></affiliation></author><author><name sortKey="Motsinger Reif, Alison" sort="Motsinger Reif, Alison" uniqKey="Motsinger Reif A" first="Alison" last="Motsinger-Reif">Alison Motsinger-Reif</name><affiliation><nlm:aff id="A2">Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, NC, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Bioinformatics Research Center, Department of Statistics, North Carolina State University, Raleigh, NC, USA</nlm:aff></affiliation></author><author><name sortKey="Lindblad Toh, Kerstin" sort="Lindblad Toh, Kerstin" uniqKey="Lindblad Toh K" first="Kerstin" last="Lindblad-Toh">Kerstin Lindblad-Toh</name><affiliation><nlm:aff id="A5">Broad Institute, Cambridge, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden</nlm:aff></affiliation></author><author><name sortKey="Modiano, Jaime F" sort="Modiano, Jaime F" uniqKey="Modiano J" first="Jaime F." last="Modiano">Jaime F. Modiano</name><affiliation><nlm:aff id="A7">Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A8">Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN, USA</nlm:aff></affiliation></author><author><name sortKey="Breen, Matthew" sort="Breen, Matthew" uniqKey="Breen M" first="Matthew" last="Breen">Matthew Breen</name><affiliation><nlm:aff id="A1">Department of Molecular Biomedical Sciences, North Carolina State University College of Veterinary Medicine; Raleigh, NC, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, NC, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Cancer Genetics Program, University of North Carolina Lineberger Comprehensive Cancer Center, Raleigh, NC, USA</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24599718</idno><idno type="pmc">5518683</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5518683</idno><idno type="RBID">PMC:5518683</idno><idno type="doi">10.1007/s10577-014-9406-z</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">003965</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">003965</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Genomic profiling reveals extensive heterogeneity in somatic DNA copy number aberrations of canine hemangiosarcoma</title><author><name sortKey="Thomas, Rachael" sort="Thomas, Rachael" uniqKey="Thomas R" first="Rachael" last="Thomas">Rachael Thomas</name><affiliation><nlm:aff id="A1">Department of Molecular Biomedical Sciences, North Carolina State University College of Veterinary Medicine; Raleigh, NC, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, NC, USA</nlm:aff></affiliation></author><author><name sortKey="Borst, Luke" sort="Borst, Luke" uniqKey="Borst L" first="Luke" last="Borst">Luke Borst</name><affiliation><nlm:aff id="A2">Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, NC, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Department of Population Health and Pathobiology, North Carolina State University College of Veterinary Medicine, Raleigh, NC, USA</nlm:aff></affiliation></author><author><name sortKey="Rotroff, Daniel" sort="Rotroff, Daniel" uniqKey="Rotroff D" first="Daniel" last="Rotroff">Daniel Rotroff</name><affiliation><nlm:aff id="A4">Bioinformatics Research Center, Department of Statistics, North Carolina State University, Raleigh, NC, USA</nlm:aff></affiliation></author><author><name sortKey="Motsinger Reif, Alison" sort="Motsinger Reif, Alison" uniqKey="Motsinger Reif A" first="Alison" last="Motsinger-Reif">Alison Motsinger-Reif</name><affiliation><nlm:aff id="A2">Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, NC, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Bioinformatics Research Center, Department of Statistics, North Carolina State University, Raleigh, NC, USA</nlm:aff></affiliation></author><author><name sortKey="Lindblad Toh, Kerstin" sort="Lindblad Toh, Kerstin" uniqKey="Lindblad Toh K" first="Kerstin" last="Lindblad-Toh">Kerstin Lindblad-Toh</name><affiliation><nlm:aff id="A5">Broad Institute, Cambridge, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden</nlm:aff></affiliation></author><author><name sortKey="Modiano, Jaime F" sort="Modiano, Jaime F" uniqKey="Modiano J" first="Jaime F." last="Modiano">Jaime F. Modiano</name><affiliation><nlm:aff id="A7">Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A8">Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN, USA</nlm:aff></affiliation></author><author><name sortKey="Breen, Matthew" sort="Breen, Matthew" uniqKey="Breen M" first="Matthew" last="Breen">Matthew Breen</name><affiliation><nlm:aff id="A1">Department of Molecular Biomedical Sciences, North Carolina State University College of Veterinary Medicine; Raleigh, NC, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, NC, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A9">Cancer Genetics Program, University of North Carolina Lineberger Comprehensive Cancer Center, Raleigh, NC, USA</nlm:aff></affiliation></author></analytic><series><title level="j">Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology</title><idno type="ISSN">0967-3849</idno><idno type="eISSN">1573-6849</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Canine hemangiosarcoma is a highly aggressive vascular neoplasm associated with extensive clinical and anatomical heterogeneity and a grave prognosis. Comprehensive molecular characterization of hemangiosarcoma may identify novel therapeutic targets and advanced clinical management strategies, but there are no published reports of tumor-associated genome instability and disrupted gene dosage in this cancer. We performed genome-wide microarray-based somatic DNA copy number profiling of 75 primary intra-abdominal hemangiosarcomas from five popular dog breeds that are highly predisposed to this disease. The cohort exhibited limited global genomic instability, compared to other canine sarcomas studied to date, and DNA copy number aberrations (CNAs) were predominantly of low amplitude. Recurrent imbalances of several key cancer-associated genes were evident; however the global penetrance of any single CNA was low and no distinct hallmark aberrations were evident. Copy number gains of dog chromosomes 13, 24 and 31, and loss of chromosome 16, were the most recurrent CNAs involving large chromosome regions, but their relative distribution within and between cases suggests they most likely represent passenger aberrations. CNAs involving <italic>CDKN2A</italic>, <italic>VEGFA</italic> and the <italic>SKI</italic> oncogene were identified as potential driver aberrations of hemangiosarcoma development, highlighting potential targets for therapeutic modulation. CNA profiles were broadly conserved between the five breeds, although subregional variation was evident, including a near two-fold lower incidence of V<italic>EGFA</italic> gain in Golden Retrievers versus other breeds (22% versus 40%). These observations support prior transcriptional studies suggesting that the clinical heterogeneity of this cancer may reflect the existence of multiple, molecularly-distinct subtypes of canine hemangiosarcoma.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">9313452</journal-id><journal-id journal-id-type="pubmed-jr-id">8478</journal-id><journal-id journal-id-type="nlm-ta">Chromosome Res</journal-id><journal-id journal-id-type="iso-abbrev">Chromosome Res.</journal-id><journal-title-group><journal-title>Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology</journal-title></journal-title-group><issn pub-type="ppub">0967-3849</issn><issn pub-type="epub">1573-6849</issn></journal-meta><article-meta><article-id pub-id-type="pmid">24599718</article-id><article-id pub-id-type="pmc">5518683</article-id><article-id pub-id-type="doi">10.1007/s10577-014-9406-z</article-id><article-id pub-id-type="manuscript">NIHMS880723</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Genomic profiling reveals extensive heterogeneity in somatic DNA copy number aberrations of canine hemangiosarcoma</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Thomas</surname><given-names>Rachael</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Borst</surname><given-names>Luke</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Rotroff</surname><given-names>Daniel</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Motsinger-Reif</surname><given-names>Alison</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Lindblad-Toh</surname><given-names>Kerstin</given-names></name><xref ref-type="aff" rid="A5">5</xref><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Modiano</surname><given-names>Jaime F.</given-names></name><xref ref-type="aff" rid="A7">7</xref><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Breen</surname><given-names>Matthew</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A9">9</xref></contrib></contrib-group><aff id="A1"><label>1</label>Department of Molecular Biomedical Sciences, North Carolina State University College of Veterinary Medicine; Raleigh, NC, USA</aff><aff id="A2"><label>2</label>Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, NC, USA</aff><aff id="A3"><label>3</label>Department of Population Health and Pathobiology, North Carolina State University College of Veterinary Medicine, Raleigh, NC, USA</aff><aff id="A4"><label>4</label>Bioinformatics Research Center, Department of Statistics, North Carolina State University, Raleigh, NC, USA</aff><aff id="A5"><label>5</label>Broad Institute, Cambridge, MA, USA</aff><aff id="A6"><label>6</label>Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden</aff><aff id="A7"><label>7</label>Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA</aff><aff id="A8"><label>8</label>Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN, USA</aff><aff id="A9"><label>9</label>Cancer Genetics Program, University of North Carolina Lineberger Comprehensive Cancer Center, Raleigh, NC, USA</aff><author-notes><corresp id="FN1">Corresponding author: Matthew Breen, Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, North Carolina 27607 USA, ph: +1-919-513-1467, fax: +1-919-513-7301, <email>Matthew_Breen@ncsu.edu</email></corresp></author-notes><pub-date pub-type="nihms-submitted"><day>2</day><month>6</month><year>2017</year></pub-date><pub-date pub-type="epub"><day>06</day><month>3</month><year>2014</year></pub-date><pub-date pub-type="ppub"><month>9</month><year>2014</year></pub-date><pub-date pub-type="pmc-release"><day>20</day><month>7</month><year>2017</year></pub-date><volume>22</volume><issue>3</issue><fpage>305</fpage><lpage>319</lpage><pmc-comment>elocation-id from pubmed: 10.1007/s10577-014-9406-z</pmc-comment>
<abstract><p id="P1">Canine hemangiosarcoma is a highly aggressive vascular neoplasm associated with extensive clinical and anatomical heterogeneity and a grave prognosis. Comprehensive molecular characterization of hemangiosarcoma may identify novel therapeutic targets and advanced clinical management strategies, but there are no published reports of tumor-associated genome instability and disrupted gene dosage in this cancer. We performed genome-wide microarray-based somatic DNA copy number profiling of 75 primary intra-abdominal hemangiosarcomas from five popular dog breeds that are highly predisposed to this disease. The cohort exhibited limited global genomic instability, compared to other canine sarcomas studied to date, and DNA copy number aberrations (CNAs) were predominantly of low amplitude. Recurrent imbalances of several key cancer-associated genes were evident; however the global penetrance of any single CNA was low and no distinct hallmark aberrations were evident. Copy number gains of dog chromosomes 13, 24 and 31, and loss of chromosome 16, were the most recurrent CNAs involving large chromosome regions, but their relative distribution within and between cases suggests they most likely represent passenger aberrations. CNAs involving <italic>CDKN2A</italic>, <italic>VEGFA</italic> and the <italic>SKI</italic> oncogene were identified as potential driver aberrations of hemangiosarcoma development, highlighting potential targets for therapeutic modulation. CNA profiles were broadly conserved between the five breeds, although subregional variation was evident, including a near two-fold lower incidence of V<italic>EGFA</italic> gain in Golden Retrievers versus other breeds (22% versus 40%). These observations support prior transcriptional studies suggesting that the clinical heterogeneity of this cancer may reflect the existence of multiple, molecularly-distinct subtypes of canine hemangiosarcoma.</p></abstract><kwd-group><kwd>canine</kwd><kwd>chromosome</kwd><kwd>hemangiosarcoma</kwd><kwd>comparative genomic hybridization (CGH)</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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