Key Roles for MYC, KIT and RET signaling in secondary angiosarcomas
Identifieur interne : 006809 ( Ncbi/Merge ); précédent : 006808; suivant : 006810Key Roles for MYC, KIT and RET signaling in secondary angiosarcomas
Auteurs : E. Styring [Suède] ; J. Seinen [Pays-Bas] ; M. Dominguez-Valentin [Suède] ; H A Domanski [Suède] ; M. Jönsson [Suède] ; F V Von Steyern [Suède] ; H J Hoekstra [Pays-Bas] ; A J H. Suurmeijer [Pays-Bas] ; M. Nilbert [Suède, Danemark]Source :
- British Journal of Cancer [ 0007-0920 ] ; 2014.
Abstract
Angiosarcomas may develop as primary tumours of unknown cause or as secondary tumours, most commonly following radiotherapy to the involved field. The different causative agents may be linked to alternate tumorigenesis, which led us to investigate the genetic profiles of morphologically indistinguishable primary and secondary angiosarcomas.
Whole-genome (18k) c-DNA-mediated annealing, selection, extension and ligation analysis was used to genetically profile 26 primary and 29 secondary angiosarcomas. Key findings were thereafter validated using RT–qPCR, immunohistochemistry and validation of the gene signature to an external data set.
In total, 103 genes were significantly deregulated between primary and secondary angiosarcomas. Secondary angiosarcomas showed upregulation of
Upregulation of
Url:
DOI: 10.1038/bjc.2014.359
PubMed: 24983371
PubMed Central: 4102954
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Key Roles for <italic>MYC</italic>, <italic>KIT</italic> and <italic>RET</italic> signaling in secondary angiosarcomas</title><author><name sortKey="Styring, E" sort="Styring, E" uniqKey="Styring E" first="E" last="Styring">E. Styring</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Orthopedics, Section III, Clinical Sciences, Lund University</institution>, 22185 Lund,<country>Sweden</country></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Oncology, Section V, Clinical Sciences, Lund University</institution>, 22185 Lund,<country>Sweden</country></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Seinen, J" sort="Seinen, J" uniqKey="Seinen J" first="J" last="Seinen">J. Seinen</name><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Division of Surgical Oncology, Department of Surgery, University Medical Center Groningen, University of Groningen</institution>, Hanzeplein 1, PO Box 30.001, 9700 Groningen,<country>The Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Dominguez Valentin, M" sort="Dominguez Valentin, M" uniqKey="Dominguez Valentin M" first="M" last="Dominguez-Valentin">M. Dominguez-Valentin</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Oncology, Section V, Clinical Sciences, Lund University</institution>, 22185 Lund,<country>Sweden</country></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Domanski, H A" sort="Domanski, H A" uniqKey="Domanski H" first="H A" last="Domanski">H A Domanski</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Department of Pathology, Section V, Clinical Sciences, Lund University</institution>, 22185 Lund,<country>Sweden</country></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Jonsson, M" sort="Jonsson, M" uniqKey="Jonsson M" first="M" last="Jönsson">M. Jönsson</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Oncology, Section V, Clinical Sciences, Lund University</institution>, 22185 Lund,<country>Sweden</country></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Von Steyern, F V" sort="Von Steyern, F V" uniqKey="Von Steyern F" first="F V" last="Von Steyern">F V Von Steyern</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Orthopedics, Section III, Clinical Sciences, Lund University</institution>, 22185 Lund,<country>Sweden</country></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hoekstra, H J" sort="Hoekstra, H J" uniqKey="Hoekstra H" first="H J" last="Hoekstra">H J Hoekstra</name><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Division of Surgical Oncology, Department of Surgery, University Medical Center Groningen, University of Groningen</institution>, Hanzeplein 1, PO Box 30.001, 9700 Groningen,<country>The Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Suurmeijer, A J H" sort="Suurmeijer, A J H" uniqKey="Suurmeijer A" first="A J H" last="Suurmeijer">A J H. Suurmeijer</name><affiliation wicri:level="1"><nlm:aff id="aff5"><institution>Department of Pathology, University Medical Center Groningen, University of Groningen</institution>, Hanzeplein 1, PO Box 30.001, 9700 Groningen,<country>The Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Nilbert, M" sort="Nilbert, M" uniqKey="Nilbert M" first="M" last="Nilbert">M. Nilbert</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Oncology, Section V, Clinical Sciences, Lund University</institution>, 22185 Lund,<country>Sweden</country></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff6"><institution>Clinical Research Centre, Hvidovre Hospital, Copenhagen University</institution>, 2650 Hvidovre,<country>Denmark</country></nlm:aff><country xml:lang="fr">Danemark</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24983371</idno><idno type="pmc">4102954</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4102954</idno><idno type="RBID">PMC:4102954</idno><idno type="doi">10.1038/bjc.2014.359</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000084</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000084</idno><idno type="wicri:Area/Pmc/Curation">000084</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000084</idno><idno type="wicri:Area/Pmc/Checkpoint">001A66</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">001A66</idno><idno type="wicri:Area/Ncbi/Merge">006809</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Key Roles for <italic>MYC</italic>, <italic>KIT</italic> and <italic>RET</italic> signaling in secondary angiosarcomas</title><author><name sortKey="Styring, E" sort="Styring, E" uniqKey="Styring E" first="E" last="Styring">E. Styring</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Orthopedics, Section III, Clinical Sciences, Lund University</institution>, 22185 Lund,<country>Sweden</country></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Oncology, Section V, Clinical Sciences, Lund University</institution>, 22185 Lund,<country>Sweden</country></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Seinen, J" sort="Seinen, J" uniqKey="Seinen J" first="J" last="Seinen">J. Seinen</name><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Division of Surgical Oncology, Department of Surgery, University Medical Center Groningen, University of Groningen</institution>, Hanzeplein 1, PO Box 30.001, 9700 Groningen,<country>The Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Dominguez Valentin, M" sort="Dominguez Valentin, M" uniqKey="Dominguez Valentin M" first="M" last="Dominguez-Valentin">M. Dominguez-Valentin</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Oncology, Section V, Clinical Sciences, Lund University</institution>, 22185 Lund,<country>Sweden</country></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Domanski, H A" sort="Domanski, H A" uniqKey="Domanski H" first="H A" last="Domanski">H A Domanski</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Department of Pathology, Section V, Clinical Sciences, Lund University</institution>, 22185 Lund,<country>Sweden</country></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Jonsson, M" sort="Jonsson, M" uniqKey="Jonsson M" first="M" last="Jönsson">M. Jönsson</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Oncology, Section V, Clinical Sciences, Lund University</institution>, 22185 Lund,<country>Sweden</country></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Von Steyern, F V" sort="Von Steyern, F V" uniqKey="Von Steyern F" first="F V" last="Von Steyern">F V Von Steyern</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Orthopedics, Section III, Clinical Sciences, Lund University</institution>, 22185 Lund,<country>Sweden</country></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hoekstra, H J" sort="Hoekstra, H J" uniqKey="Hoekstra H" first="H J" last="Hoekstra">H J Hoekstra</name><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Division of Surgical Oncology, Department of Surgery, University Medical Center Groningen, University of Groningen</institution>, Hanzeplein 1, PO Box 30.001, 9700 Groningen,<country>The Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Suurmeijer, A J H" sort="Suurmeijer, A J H" uniqKey="Suurmeijer A" first="A J H" last="Suurmeijer">A J H. Suurmeijer</name><affiliation wicri:level="1"><nlm:aff id="aff5"><institution>Department of Pathology, University Medical Center Groningen, University of Groningen</institution>, Hanzeplein 1, PO Box 30.001, 9700 Groningen,<country>The Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Nilbert, M" sort="Nilbert, M" uniqKey="Nilbert M" first="M" last="Nilbert">M. Nilbert</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Oncology, Section V, Clinical Sciences, Lund University</institution>, 22185 Lund,<country>Sweden</country></nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff6"><institution>Clinical Research Centre, Hvidovre Hospital, Copenhagen University</institution>, 2650 Hvidovre,<country>Denmark</country></nlm:aff><country xml:lang="fr">Danemark</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">British Journal of Cancer</title><idno type="ISSN">0007-0920</idno><idno type="eISSN">1532-1827</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background:</title><p>Angiosarcomas may develop as primary tumours of unknown cause or as secondary tumours, most commonly following radiotherapy to the involved field. The different causative agents may be linked to alternate tumorigenesis, which led us to investigate the genetic profiles of morphologically indistinguishable primary and secondary angiosarcomas.</p></sec><sec><title>Methods:</title><p>Whole-genome (18k) c-DNA-mediated annealing, selection, extension and ligation analysis was used to genetically profile 26 primary and 29 secondary angiosarcomas. Key findings were thereafter validated using RT–qPCR, immunohistochemistry and validation of the gene signature to an external data set.</p></sec><sec><title>Results:</title><p>In total, 103 genes were significantly deregulated between primary and secondary angiosarcomas. Secondary angiosarcomas showed upregulation of <italic>MYC, KIT</italic> and <italic>RET</italic> and downregulation of <italic>CDKN2C</italic>. Functional annotation analysis identified multiple target genes in the receptor protein tyrosine kinase pathway. The results were validated using RT–qPCR and immunohistochemistry. Further, the gene signature was applied to an external data set and, herein, distinguished primary from secondary angiosarcomas.</p></sec><sec><title>Conclusions:</title><p>Upregulation of <italic>MYC</italic>, <italic>KIT</italic> and <italic>RET</italic> and downregulation of <italic>CDKN2C</italic> characterise secondary angiosarcoma, which implies possibilities for diagnostic application and a mechanistic basis for therapeutic evaluation of RET-kinase-inhibitors in these highly aggressive tumours.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Antonescu, Cr" uniqKey="Antonescu C">CR Antonescu</name></author><author><name sortKey="Yoshida, A" uniqKey="Yoshida A">A Yoshida</name></author><author><name sortKey="Guo, T" uniqKey="Guo T">T Guo</name></author><author><name sortKey="Chang, Ne" uniqKey="Chang N">NE Chang</name></author><author><name sortKey="Zhang, L" uniqKey="Zhang L">L Zhang</name></author><author><name 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Br J Cancer</journal-id><journal-id journal-id-type="iso-abbrev">Br. J. Cancer</journal-id><journal-title-group><journal-title>British Journal of Cancer</journal-title></journal-title-group><issn pub-type="ppub">0007-0920</issn><issn pub-type="epub">1532-1827</issn><publisher><publisher-name>Nature Publishing Group</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">24983371</article-id><article-id pub-id-type="pmc">4102954</article-id><article-id pub-id-type="pii">bjc2014359</article-id><article-id pub-id-type="doi">10.1038/bjc.2014.359</article-id><article-categories><subj-group subj-group-type="heading"><subject>Genetics and Genomics</subject></subj-group></article-categories><title-group><article-title>Key Roles for <italic>MYC</italic>, <italic>KIT</italic> and <italic>RET</italic> signaling in secondary angiosarcomas</article-title><alt-title alt-title-type="running">Genetic profiles in secondary angiosarcoma</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Styring</surname><given-names>E</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="corresp" rid="caf1">*</xref></contrib><contrib contrib-type="author"><name><surname>Seinen</surname><given-names>J</given-names></name><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Dominguez-Valentin</surname><given-names>M</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Domanski</surname><given-names>H A</given-names></name><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Jönsson</surname><given-names>M</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>von Steyern</surname><given-names>F V</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Hoekstra</surname><given-names>H J</given-names></name><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Suurmeijer</surname><given-names>A J H</given-names></name><xref ref-type="aff" rid="aff5">5</xref></contrib><contrib contrib-type="author"><name><surname>Nilbert</surname><given-names>M</given-names></name><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff6">6</xref></contrib><aff id="aff1"><label>1</label><institution>Department of Orthopedics, Section III, Clinical Sciences, Lund University</institution>, 22185 Lund,<country>Sweden</country></aff><aff id="aff2"><label>2</label><institution>Department of Oncology, Section V, Clinical Sciences, Lund University</institution>, 22185 Lund,<country>Sweden</country></aff><aff id="aff3"><label>3</label><institution>Division of Surgical Oncology, Department of Surgery, University Medical Center Groningen, University of Groningen</institution>, Hanzeplein 1, PO Box 30.001, 9700 Groningen,<country>The Netherlands</country></aff><aff id="aff4"><label>4</label><institution>Department of Pathology, Section V, Clinical Sciences, Lund University</institution>, 22185 Lund,<country>Sweden</country></aff><aff id="aff5"><label>5</label><institution>Department of Pathology, University Medical Center Groningen, University of Groningen</institution>, Hanzeplein 1, PO Box 30.001, 9700 Groningen,<country>The Netherlands</country></aff><aff id="aff6"><label>6</label><institution>Clinical Research Centre, Hvidovre Hospital, Copenhagen University</institution>, 2650 Hvidovre,<country>Denmark</country></aff></contrib-group><author-notes><corresp id="caf1"><label>*</label>E-mail: <email>emelie.styring@med.lu.se</email></corresp></author-notes><pub-date pub-type="ppub"><day>15</day><month>07</month><year>2014</year></pub-date><pub-date pub-type="epub"><day>01</day><month>07</month><year>2014</year></pub-date><volume>111</volume><issue>2</issue><fpage>407</fpage><lpage>412</lpage><history><date date-type="received"><day>23</day><month>11</month><year>2013</year></date><date date-type="rev-recd"><day>26</day><month>05</month><year>2014</year></date><date date-type="accepted"><day>01</day><month>06</month><year>2014</year></date></history><permissions><copyright-statement>Copyright © 2014 Cancer Research UK</copyright-statement><copyright-year>2014</copyright-year><copyright-holder>Cancer Research UK</copyright-holder><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc-sa/3.0/"><license-p>From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/</license-p></license></permissions><abstract><sec><title>Background:</title><p>Angiosarcomas may develop as primary tumours of unknown cause or as secondary tumours, most commonly following radiotherapy to the involved field. The different causative agents may be linked to alternate tumorigenesis, which led us to investigate the genetic profiles of morphologically indistinguishable primary and secondary angiosarcomas.</p></sec><sec><title>Methods:</title><p>Whole-genome (18k) c-DNA-mediated annealing, selection, extension and ligation analysis was used to genetically profile 26 primary and 29 secondary angiosarcomas. Key findings were thereafter validated using RT–qPCR, immunohistochemistry and validation of the gene signature to an external data set.</p></sec><sec><title>Results:</title><p>In total, 103 genes were significantly deregulated between primary and secondary angiosarcomas. Secondary angiosarcomas showed upregulation of <italic>MYC, KIT</italic> and <italic>RET</italic> and downregulation of <italic>CDKN2C</italic>. Functional annotation analysis identified multiple target genes in the receptor protein tyrosine kinase pathway. The results were validated using RT–qPCR and immunohistochemistry. Further, the gene signature was applied to an external data set and, herein, distinguished primary from secondary angiosarcomas.</p></sec><sec><title>Conclusions:</title><p>Upregulation of <italic>MYC</italic>, <italic>KIT</italic> and <italic>RET</italic> and downregulation of <italic>CDKN2C</italic> characterise secondary angiosarcoma, which implies possibilities for diagnostic application and a mechanistic basis for therapeutic evaluation of RET-kinase-inhibitors in these highly aggressive tumours.</p></sec></abstract><kwd-group><kwd>tyrosine kinase receptor</kwd><kwd>KDR</kwd><kwd>radiation-associated</kwd><kwd>gene expression</kwd><kwd>CDKN2C</kwd><kwd>MYC</kwd><kwd>KIT</kwd></kwd-group></article-meta></front><floats-group><fig id="fig1"><label>Figure 1</label><caption><p><bold>Unsupervised hierarchical clustering of the 28 primary (green) and 34 secondary (blue) angiosarcomas (X-axis).</bold> Samples with similar gene expression profiles cluster together. The full heat map is available upon request from the corresponding author.</p></caption><graphic xlink:href="bjc2014359f1"></graphic></fig><fig id="fig2"><label>Figure 2</label><caption><p><bold>Heat map (SAM analysis) of the 103 genes (Y-axis) expressed at significantly different levels between 28 primary (green) and 24 secondary (blue) angiosarcomas.</bold> Samples with similar gene expression profiles cluster together on the X-axis. Upregulated expression is marked with red, and downregulated with green and black reflects no difference in expression levels.</p></caption><graphic xlink:href="bjc2014359f2"></graphic></fig><fig id="fig3"><label>Figure 3</label><caption><p><bold>Scatterplots demonstrating the RT–qPCR expression ratios (Y-axis) in primary and secondary angiosarcomas (X-axis) in relation to the pooled reference genes.</bold> In secondary angiosarcoma upregulation affects (<bold>A</bold>) MYC and (<bold>B</bold>) RET, whereas downregulation is demonstrated for (<bold>C</bold>) CDKN2C.</p></caption><graphic xlink:href="bjc2014359f3"></graphic></fig><fig id="fig4"><label>Figure 4</label><caption><p><bold>Immunohistochemical staining for KDR</bold> Immunohistochemical staining for KDR in (<bold>A</bold>) a primary angiosarcoma with low expression, <20% of the cells positive; (<bold>B</bold>) secondary angiosarcoma with intermediate expression, ⩾20% but <75% (<bold>C</bold>) secondary angiosarcoma with high expression, immunoreactivity>75% of the cells. Grading was performed according to <xref ref-type="bibr" rid="bib1">Antonescu <italic>et al</italic>, (2009)</xref>. The expression intensities were determined in the areas with highest staining intensity.</p></caption><graphic xlink:href="bjc2014359f4"></graphic></fig><fig id="fig5"><label>Figure 5</label><caption><p><bold>Heat map and hierarchical clustering of our 103-gene signature applied to the external data set E-MEXP-3271 (<xref ref-type="bibr" rid="bib13">Hadj-Hamou <italic>et al</italic>, 2012</xref>).</bold> Distinct separation is obtained between primary (green) and secondary (blue) angiosarcomas. Samples with similar gene expression profiles cluster together; red: upregualted expression, green: downregulated expression, black: no difference in expression levels.</p></caption><graphic xlink:href="bjc2014359f5"></graphic></fig><table-wrap id="tbl1"><label>Table 1</label><caption><title>Summary of clinical characteristics</title></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="left"></col><col align="left"></col></colgroup><thead valign="bottom"><tr><th align="left" valign="top" charoff="50"> </th><th align="center" valign="top" charoff="50"><bold>Primary angiosarcomas</bold></th><th align="left" valign="top" charoff="50"><bold>Secondary angiosarcomas</bold></th></tr></thead><tbody valign="top"><tr><td align="left" valign="top" charoff="50">Number of patients<hr></hr></td><td align="left" valign="top" charoff="50">26<hr></hr></td><td align="left" valign="top" charoff="50">29<hr></hr></td></tr><tr><td align="left" valign="top" charoff="50">Age at diagnosis (median, range)<hr></hr></td><td align="left" valign="top" charoff="50">68 (3–91)<hr></hr></td><td align="left" valign="top" charoff="50">68 (50–90)<hr></hr></td></tr><tr><td align="left" valign="top" charoff="50">Sex (f/m)<hr></hr></td><td align="left" valign="top" charoff="50">16/10<hr></hr></td><td align="left" valign="top" charoff="50">29/0<hr></hr></td></tr><tr><td colspan="3" align="left" valign="top" charoff="50"><bold>Location</bold><hr></hr></td></tr><tr><td align="left" valign="top" charoff="50">Head and neck</td><td align="left" valign="top" charoff="50">6</td><td align="left" valign="top" charoff="50">—</td></tr><tr><td align="left" valign="top" charoff="50">Upper extremity</td><td align="left" valign="top" charoff="50">3</td><td align="left" valign="top" charoff="50">2</td></tr><tr><td align="left" valign="top" charoff="50">Thoracical wall</td><td align="left" valign="top" charoff="50">5</td><td align="left" valign="top" charoff="50">27</td></tr><tr><td align="left" valign="top" charoff="50">Lower extremity</td><td align="left" valign="top" charoff="50">4</td><td align="left" valign="top" charoff="50">—</td></tr><tr><td align="left" valign="top" charoff="50">Other locations<hr></hr></td><td align="left" valign="top" charoff="50">8<hr></hr></td><td align="left" valign="top" charoff="50">—<hr></hr></td></tr><tr><td align="left" valign="top" charoff="50">Median years between breast cancer and angiosarcoma</td><td align="left" valign="top" charoff="50">—</td><td align="left" valign="top" charoff="50">8 (4–20)</td></tr></tbody></table><table-wrap-foot><fn id="t1-fn1"><p>Abbreviations: f=female; m=male.</p></fn></table-wrap-foot></table-wrap><table-wrap id="tbl2"><label>Table 2</label><caption><title>Selected deregulated genes with their respective fold changes</title></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="left"></col><col align="center"></col><col align="center"></col></colgroup><thead valign="bottom"><tr><th align="left" valign="top" charoff="50"><bold>Gene</bold></th><th align="left" valign="top" charoff="50"><bold>Definition</bold></th><th align="center" valign="top" charoff="50"><bold>Chromosome</bold></th><th align="center" valign="top" charoff="50"><bold>Fold change</bold></th></tr></thead><tbody valign="top"><tr><td align="left" valign="top" charoff="50"><italic>MYC</italic><hr></hr></td><td align="left" valign="top" charoff="50"><italic>V-myc</italic> myelocytomatosis viral oncogene homologue<hr></hr></td><td align="center" valign="top" charoff="50">8<hr></hr></td><td align="center" valign="top" charoff="50">3.7<hr></hr></td></tr><tr><td align="left" valign="top" charoff="50"><italic>RET</italic><hr></hr></td><td align="left" valign="top" charoff="50"><italic>Ret</italic> proto-oncogene (<italic>RET-ELE1, MEN2A, MEN2B, RET51</italic>)<hr></hr></td><td align="center" valign="top" charoff="50">10<hr></hr></td><td align="center" valign="top" charoff="50">3.0<hr></hr></td></tr><tr><td align="left" valign="top" charoff="50"><italic>KIT</italic><hr></hr></td><td align="left" valign="top" charoff="50"><italic>V-kit</italic> Hardy-Zuckerman 4 feline sarcoma viral oncogene homologue (<italic>CD117, C-KIT</italic>)<hr></hr></td><td align="center" valign="top" charoff="50">4<hr></hr></td><td align="center" valign="top" charoff="50">2.1<hr></hr></td></tr><tr><td align="left" valign="top" charoff="50"><italic>FLT4</italic><hr></hr></td><td align="left" valign="top" charoff="50">Fms-related tyrosine kinase 4 (FLT4)<hr></hr></td><td align="center" valign="top" charoff="50">5<hr></hr></td><td align="center" valign="top" charoff="50">2.0<hr></hr></td></tr><tr><td align="left" valign="top" charoff="50"><italic>CDKN2C</italic></td><td align="left" valign="top" charoff="50">Cyclin-dependent kinase inhibitor 2C (<italic>INK4C, p18</italic>)</td><td align="center" valign="top" charoff="50">1</td><td align="center" valign="top" charoff="50">0.5</td></tr></tbody></table><table-wrap-foot><fn id="t2-fn1"><p>Abbreviation: MEN2=multiple endocrine neoplasia type 2.</p></fn></table-wrap-foot></table-wrap></floats-group></pmc><affiliations><list><country><li>Danemark</li><li>Pays-Bas</li><li>Suède</li></country></list><tree><country name="Suède"><noRegion><name sortKey="Styring, E" sort="Styring, E" uniqKey="Styring E" first="E" last="Styring">E. Styring</name></noRegion><name sortKey="Domanski, H A" sort="Domanski, H A" uniqKey="Domanski H" first="H A" last="Domanski">H A Domanski</name><name sortKey="Dominguez Valentin, M" sort="Dominguez Valentin, M" uniqKey="Dominguez Valentin M" first="M" last="Dominguez-Valentin">M. Dominguez-Valentin</name><name sortKey="Jonsson, M" sort="Jonsson, M" uniqKey="Jonsson M" first="M" last="Jönsson">M. Jönsson</name><name sortKey="Nilbert, M" sort="Nilbert, M" uniqKey="Nilbert M" first="M" last="Nilbert">M. Nilbert</name><name sortKey="Styring, E" sort="Styring, E" uniqKey="Styring E" first="E" last="Styring">E. Styring</name><name sortKey="Von Steyern, F V" sort="Von Steyern, F V" uniqKey="Von Steyern F" first="F V" last="Von Steyern">F V Von Steyern</name></country><country name="Pays-Bas"><noRegion><name sortKey="Seinen, J" sort="Seinen, J" uniqKey="Seinen J" first="J" last="Seinen">J. Seinen</name></noRegion><name sortKey="Hoekstra, H J" sort="Hoekstra, H J" uniqKey="Hoekstra H" first="H J" last="Hoekstra">H J Hoekstra</name><name sortKey="Suurmeijer, A J H" sort="Suurmeijer, A J H" uniqKey="Suurmeijer A" first="A J H" last="Suurmeijer">A J H. Suurmeijer</name></country><country name="Danemark"><noRegion><name sortKey="Nilbert, M" sort="Nilbert, M" uniqKey="Nilbert M" first="M" last="Nilbert">M. Nilbert</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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