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MYC High Level Gene Amplification Is a Distinctive Feature of Angiosarcomas after Irradiation or Chronic Lymphedema

Identifieur interne : 001E61 ( Pmc/Corpus ); précédent : 001E60; suivant : 001E62

MYC High Level Gene Amplification Is a Distinctive Feature of Angiosarcomas after Irradiation or Chronic Lymphedema

Auteurs : Johanna Manner ; Bernhard Radlwimmer ; Peter Hohenberger ; Katharina Mössinger ; Stefan Küffer ; Christian Sauer ; Djeda Belharazem ; Andreas Zettl ; Jean-Michel Coindre ; Christian Hallermann ; Jörg Thomas Hartmann ; Detlef Katenkamp ; Kathrin Katenkamp ; Patrick Schöffski ; Raf Sciot ; Agnieszka Wozniak ; Peter Lichter ; Alexander Marx ; Philipp Ströbel

Source :

RBID : PMC:2797867

Abstract

Angiosarcomas (AS) are rare vascular malignancies that arise either de novo as primary tumors or secondary to irradiation or chronic lymphedema. The cytogenetics of angiosarcomas are poorly characterized. We applied array-comparative genomic hybridization as a screening method to identify recurrent alterations in 22 cases. Recurrent genetic alterations were identified only in secondary but not in primary AS. The most frequent recurrent alterations were high level amplifications on chromosome 8q24.21 (50%), followed by 10p12.33 (33%) and 5q35.3 (11%). Fluorescence in situ hybridization analysis in 28 primary and 33 secondary angiosarcomas (31 tumors secondary to irradiation, 2 tumors secondary to chronic lymphedema) confirmed high level amplification of MYC on chromosome 8q24.21 as a recurrent genetic alteration found exclusively in 55% of AS secondary to irradiation or chronic lymphedema, but not in primary AS. Amplification of MYC did not predispose to high grade morphology or increased cell turnover. In conclusion, despite their identical morphology, secondary AS are genetically different from primary AS and are characterized by a high frequency of high level amplifications of MYC. This finding may have implications both for the diagnosis and treatment of these tumors.


Url:
DOI: 10.2353/ajpath.2010.090637
PubMed: 20008140
PubMed Central: 2797867

Links to Exploration step

PMC:2797867

Le document en format XML

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High Level Gene Amplification Is a Distinctive Feature of Angiosarcomas after Irradiation or Chronic Lymphedema</title>
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<name sortKey="Sciot, Raf" sort="Sciot, Raf" uniqKey="Sciot R" first="Raf" last="Sciot">Raf Sciot</name>
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High Level Gene Amplification Is a Distinctive Feature of Angiosarcomas after Irradiation or Chronic Lymphedema</title>
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<name sortKey="Hallermann, Christian" sort="Hallermann, Christian" uniqKey="Hallermann C" first="Christian" last="Hallermann">Christian Hallermann</name>
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<name sortKey="Hartmann, Jorg Thomas" sort="Hartmann, Jorg Thomas" uniqKey="Hartmann J" first="Jörg Thomas" last="Hartmann">Jörg Thomas Hartmann</name>
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<nlm:aff id="aff7">Department of Medical Oncology, Medical Center II, Eberhard-Karls-University, Tuebingen, Germany</nlm:aff>
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<name sortKey="Katenkamp, Detlef" sort="Katenkamp, Detlef" uniqKey="Katenkamp D" first="Detlef" last="Katenkamp">Detlef Katenkamp</name>
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<nlm:aff id="aff8">Institute of Pathology, University of Jena, Germany</nlm:aff>
</affiliation>
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<name sortKey="Katenkamp, Kathrin" sort="Katenkamp, Kathrin" uniqKey="Katenkamp K" first="Kathrin" last="Katenkamp">Kathrin Katenkamp</name>
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</affiliation>
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<name sortKey="Schoffski, Patrick" sort="Schoffski, Patrick" uniqKey="Schoffski P" first="Patrick" last="Schöffski">Patrick Schöffski</name>
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<name sortKey="Sciot, Raf" sort="Sciot, Raf" uniqKey="Sciot R" first="Raf" last="Sciot">Raf Sciot</name>
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</affiliation>
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<name sortKey="Wozniak, Agnieszka" sort="Wozniak, Agnieszka" uniqKey="Wozniak A" first="Agnieszka" last="Wozniak">Agnieszka Wozniak</name>
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<name sortKey="Marx, Alexander" sort="Marx, Alexander" uniqKey="Marx A" first="Alexander" last="Marx">Alexander Marx</name>
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<nlm:aff id="aff1">Institute of Pathology, Division of Surgical Oncology and Thoracic Surgery, University Medical Centre Mannheim, University of Heidelberg, Germany</nlm:aff>
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<name sortKey="Strobel, Philipp" sort="Strobel, Philipp" uniqKey="Strobel P" first="Philipp" last="Ströbel">Philipp Ströbel</name>
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<p>Angiosarcomas (AS) are rare vascular malignancies that arise either
<bold>
<italic>de novo</italic>
</bold>
as primary tumors or secondary to irradiation or chronic lymphedema. The cytogenetics of angiosarcomas are poorly characterized. We applied array-comparative genomic hybridization as a screening method to identify recurrent alterations in 22 cases. Recurrent genetic alterations were identified only in secondary but not in primary AS. The most frequent recurrent alterations were high level amplifications on chromosome 8q24.21 (50%), followed by 10p12.33 (33%) and 5q35.3 (11%). Fluorescence in situ hybridization analysis in 28 primary and 33 secondary angiosarcomas (31 tumors secondary to irradiation, 2 tumors secondary to chronic lymphedema) confirmed high level amplification of
<bold>
<italic>MYC</italic>
</bold>
on chromosome 8q24.21 as a recurrent genetic alteration found exclusively in 55% of AS secondary to irradiation or chronic lymphedema, but not in primary AS. Amplification of
<bold>
<italic>MYC</italic>
</bold>
did not predispose to high grade morphology or increased cell turnover. In conclusion, despite their identical morphology, secondary AS are genetically different from primary AS and are characterized by a high frequency of high level amplifications of
<bold>
<italic>MYC</italic>
</bold>
. This finding may have implications both for the diagnosis and treatment of these tumors.</p>
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<italic>MYC</italic>
High Level Gene Amplification Is a Distinctive Feature of Angiosarcomas after Irradiation or Chronic Lymphedema</article-title>
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<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Manner</surname>
<given-names>Johanna</given-names>
</name>
<xref rid="aff1" ref-type="aff">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Radlwimmer</surname>
<given-names>Bernhard</given-names>
</name>
<xref rid="aff3" ref-type="aff"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Hohenberger</surname>
<given-names>Peter</given-names>
</name>
<xref rid="aff2" ref-type="aff"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Mössinger</surname>
<given-names>Katharina</given-names>
</name>
<xref rid="aff1" ref-type="aff">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Küffer</surname>
<given-names>Stefan</given-names>
</name>
<xref rid="aff1" ref-type="aff">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Sauer</surname>
<given-names>Christian</given-names>
</name>
<xref rid="aff1" ref-type="aff">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Belharazem</surname>
<given-names>Djeda</given-names>
</name>
<xref rid="aff1" ref-type="aff">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Zettl</surname>
<given-names>Andreas</given-names>
</name>
<xref rid="aff4" ref-type="aff">§</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Coindre</surname>
<given-names>Jean-Michel</given-names>
</name>
<xref rid="aff5" ref-type="aff"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Hallermann</surname>
<given-names>Christian</given-names>
</name>
<xref rid="aff6" ref-type="aff"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Hartmann</surname>
<given-names>Jörg Thomas</given-names>
</name>
<xref rid="aff7" ref-type="aff">**</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Katenkamp</surname>
<given-names>Detlef</given-names>
</name>
<xref rid="aff8" ref-type="aff">††</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Katenkamp</surname>
<given-names>Kathrin</given-names>
</name>
<xref rid="aff8" ref-type="aff">††</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Schöffski</surname>
<given-names>Patrick</given-names>
</name>
<xref rid="aff9" ref-type="aff">‡‡</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Sciot</surname>
<given-names>Raf</given-names>
</name>
<xref rid="aff10" ref-type="aff">§§</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wozniak</surname>
<given-names>Agnieszka</given-names>
</name>
<xref rid="aff9" ref-type="aff">‡‡</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lichter</surname>
<given-names>Peter</given-names>
</name>
<xref rid="aff3" ref-type="aff"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Marx</surname>
<given-names>Alexander</given-names>
</name>
<xref rid="aff1" ref-type="aff">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ströbel</surname>
<given-names>Philipp</given-names>
</name>
<email>philipp.stroebel@umm.de</email>
<xref rid="aff1" ref-type="aff">*</xref>
<xref rid="cor1" ref-type="corresp">*</xref>
</contrib>
</contrib-group>
<aff id="aff1">
<label>*</label>
Institute of Pathology, Division of Surgical Oncology and Thoracic Surgery, University Medical Centre Mannheim, University of Heidelberg, Germany</aff>
<aff id="aff2">
<label></label>
Department of Surgery, Division of Surgical Oncology and Thoracic Surgery, University Medical Centre Mannheim, University of Heidelberg, Germany</aff>
<aff id="aff3">
<label></label>
German Cancer Research Center (DKFZ), Division of Molecular Genetics, Heidelberg, Germany</aff>
<aff id="aff4">
<label>§</label>
Pathology Viollier, Basle, Switzerland</aff>
<aff id="aff5">
<label></label>
Department of Pathology and INSERM U916, Institut Bergonié and Laboratory of Pathology, University Victor Ségalen, Bordeaux, France</aff>
<aff id="aff6">
<label></label>
Department of Dermatology, Fachklinik Hornheide, Münster, Germany</aff>
<aff id="aff7">
<label>**</label>
Department of Medical Oncology, Medical Center II, Eberhard-Karls-University, Tuebingen, Germany</aff>
<aff id="aff8">
<label>††</label>
Institute of Pathology, University of Jena, Germany</aff>
<aff id="aff9">
<label>‡‡</label>
Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Catholic University Leuven, Leuven, Belgium</aff>
<aff id="aff10">
<label>§§</label>
Laboratory of Morphology and Molecular Pathology, Department of Pathology, University Hospital, Catholic University of Leuven, Belgium</aff>
<author-notes>
<corresp id="cor1">
<label>*</label>
Address reprint requests to Prof. Philipp Ströbel, M.D., Institute of Pathology, University Medical Centre Mannheim, University of Heidelberg, Germany, Theodor-Kutzer-Ufer 1-3, D-68135 Mannheim
<email>philipp.stroebel@umm.de</email>
</corresp>
</author-notes>
<pub-date pub-type="ppub">
<month>1</month>
<year>2010</year>
</pub-date>
<volume>176</volume>
<issue>1</issue>
<fpage>34</fpage>
<lpage>39</lpage>
<history>
<date date-type="accepted">
<day>3</day>
<month>9</month>
<year>2009</year>
</date>
</history>
<permissions>
<copyright-statement>© 2010 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.</copyright-statement>
<copyright-year>2010</copyright-year>
<copyright-holder>American Society for Investigative Pathology</copyright-holder>
</permissions>
<abstract>
<p>Angiosarcomas (AS) are rare vascular malignancies that arise either
<bold>
<italic>de novo</italic>
</bold>
as primary tumors or secondary to irradiation or chronic lymphedema. The cytogenetics of angiosarcomas are poorly characterized. We applied array-comparative genomic hybridization as a screening method to identify recurrent alterations in 22 cases. Recurrent genetic alterations were identified only in secondary but not in primary AS. The most frequent recurrent alterations were high level amplifications on chromosome 8q24.21 (50%), followed by 10p12.33 (33%) and 5q35.3 (11%). Fluorescence in situ hybridization analysis in 28 primary and 33 secondary angiosarcomas (31 tumors secondary to irradiation, 2 tumors secondary to chronic lymphedema) confirmed high level amplification of
<bold>
<italic>MYC</italic>
</bold>
on chromosome 8q24.21 as a recurrent genetic alteration found exclusively in 55% of AS secondary to irradiation or chronic lymphedema, but not in primary AS. Amplification of
<bold>
<italic>MYC</italic>
</bold>
did not predispose to high grade morphology or increased cell turnover. In conclusion, despite their identical morphology, secondary AS are genetically different from primary AS and are characterized by a high frequency of high level amplifications of
<bold>
<italic>MYC</italic>
</bold>
. This finding may have implications both for the diagnosis and treatment of these tumors.</p>
</abstract>
</article-meta>
</front>
</pmc>
</record>

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