Alterations of p53 and PIK3CA/AKT/mTOR Pathways in Angiosarcomas: A Pattern Distinct from Other Sarcomas with Complex Genomics
Identifieur interne : 003375 ( Pmc/Corpus ); précédent : 003374; suivant : 003376Alterations of p53 and PIK3CA/AKT/mTOR Pathways in Angiosarcomas: A Pattern Distinct from Other Sarcomas with Complex Genomics
Auteurs : Antoine Italiano ; Chun-Liang Chen ; Rachael Thomas ; Matthew Breen ; Françoise Bonnet ; Nicolas Sevenet ; Michel Longy ; Robert G. Maki ; Jean-Michel Coindre ; Cristina R. AntonescuSource :
- Cancer [ 0008-543X ] ; 2012.
Abstract
The p53 and the PIK3CA/AKT/mTOR pathways are frequently altered in sarcoma with complex genomics such as leiomyosarcoma (LMS) or undifferentiated pleomorphic sarcoma (UPS). The scale of genetic abnormalities in these pathways remains unknown in angiosarcoma.
We investigated the status of critical genes involved in the p53 and the PIK3CA/AKT/mTOR pathways in a series of 62 AS.
The mutation and deletion rates of
Angiosarcomas constitute a distinct subgroup among sarcomas with complex genomics. Although
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DOI: 10.1002/cncr.27614
PubMed: 22648906
PubMed Central: 3434269
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Alterations of p53 and PIK3CA/AKT/mTOR Pathways in Angiosarcomas: A Pattern Distinct from Other Sarcomas with Complex Genomics</title><author><name sortKey="Italiano, Antoine" sort="Italiano, Antoine" uniqKey="Italiano A" first="Antoine" last="Italiano">Antoine Italiano</name><affiliation><nlm:aff id="A1">Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Medical Oncology, Institute Bergonié, Bordeaux, France</nlm:aff></affiliation></author><author><name sortKey="Chen, Chun Liang" sort="Chen, Chun Liang" uniqKey="Chen C" first="Chun-Liang" last="Chen">Chun-Liang Chen</name><affiliation><nlm:aff id="A1">Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY</nlm:aff></affiliation></author><author><name sortKey="Thomas, Rachael" sort="Thomas, Rachael" uniqKey="Thomas R" first="Rachael" last="Thomas">Rachael Thomas</name><affiliation><nlm:aff id="A3">Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, NC</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="A3">Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, NC</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Cancer Genetics Program, UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC</nlm:aff></affiliation></author><author><name sortKey="Bonnet, Francoise" sort="Bonnet, Francoise" uniqKey="Bonnet F" first="Françoise" last="Bonnet">Françoise Bonnet</name><affiliation><nlm:aff id="A6">INSERM U916, University of Bordeaux, France</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Cancer Genetics Unit, Institut Bergonié, Bordeaux, France</nlm:aff></affiliation></author><author><name sortKey="Sevenet, Nicolas" sort="Sevenet, Nicolas" uniqKey="Sevenet N" first="Nicolas" last="Sevenet">Nicolas Sevenet</name><affiliation><nlm:aff id="A6">INSERM U916, University of Bordeaux, France</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Cancer Genetics Unit, Institut Bergonié, Bordeaux, France</nlm:aff></affiliation></author><author><name sortKey="Longy, Michel" sort="Longy, Michel" uniqKey="Longy M" first="Michel" last="Longy">Michel Longy</name><affiliation><nlm:aff id="A6">INSERM U916, University of Bordeaux, France</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Cancer Genetics Unit, Institut Bergonié, Bordeaux, France</nlm:aff></affiliation></author><author><name sortKey="Maki, Robert G" sort="Maki, Robert G" uniqKey="Maki R" first="Robert G." last="Maki">Robert G. Maki</name><affiliation><nlm:aff id="A8">Department of Medicine/Pediatrics, Mount Sinai School of Medicine, New York, NY, USA</nlm:aff></affiliation></author><author><name sortKey="Coindre, Jean Michel" sort="Coindre, Jean Michel" uniqKey="Coindre J" first="Jean-Michel" last="Coindre">Jean-Michel Coindre</name><affiliation><nlm:aff id="A9">Department of Pathology, Institut Bergonié, Bordeaux, France</nlm:aff></affiliation></author><author><name sortKey="Antonescu, Cristina R" sort="Antonescu, Cristina R" uniqKey="Antonescu C" first="Cristina R." last="Antonescu">Cristina R. Antonescu</name><affiliation><nlm:aff id="A1">Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22648906</idno><idno type="pmc">3434269</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3434269</idno><idno type="RBID">PMC:3434269</idno><idno type="doi">10.1002/cncr.27614</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">003375</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">003375</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Alterations of p53 and PIK3CA/AKT/mTOR Pathways in Angiosarcomas: A Pattern Distinct from Other Sarcomas with Complex Genomics</title><author><name sortKey="Italiano, Antoine" sort="Italiano, Antoine" uniqKey="Italiano A" first="Antoine" last="Italiano">Antoine Italiano</name><affiliation><nlm:aff id="A1">Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Medical Oncology, Institute Bergonié, Bordeaux, France</nlm:aff></affiliation></author><author><name sortKey="Chen, Chun Liang" sort="Chen, Chun Liang" uniqKey="Chen C" first="Chun-Liang" last="Chen">Chun-Liang Chen</name><affiliation><nlm:aff id="A1">Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY</nlm:aff></affiliation></author><author><name sortKey="Thomas, Rachael" sort="Thomas, Rachael" uniqKey="Thomas R" first="Rachael" last="Thomas">Rachael Thomas</name><affiliation><nlm:aff id="A3">Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, NC</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="A3">Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC</nlm:aff></affiliation><affiliation><nlm:aff id="A4">Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, NC</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Cancer Genetics Program, UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC</nlm:aff></affiliation></author><author><name sortKey="Bonnet, Francoise" sort="Bonnet, Francoise" uniqKey="Bonnet F" first="Françoise" last="Bonnet">Françoise Bonnet</name><affiliation><nlm:aff id="A6">INSERM U916, University of Bordeaux, France</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Cancer Genetics Unit, Institut Bergonié, Bordeaux, France</nlm:aff></affiliation></author><author><name sortKey="Sevenet, Nicolas" sort="Sevenet, Nicolas" uniqKey="Sevenet N" first="Nicolas" last="Sevenet">Nicolas Sevenet</name><affiliation><nlm:aff id="A6">INSERM U916, University of Bordeaux, France</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Cancer Genetics Unit, Institut Bergonié, Bordeaux, France</nlm:aff></affiliation></author><author><name sortKey="Longy, Michel" sort="Longy, Michel" uniqKey="Longy M" first="Michel" last="Longy">Michel Longy</name><affiliation><nlm:aff id="A6">INSERM U916, University of Bordeaux, France</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Cancer Genetics Unit, Institut Bergonié, Bordeaux, France</nlm:aff></affiliation></author><author><name sortKey="Maki, Robert G" sort="Maki, Robert G" uniqKey="Maki R" first="Robert G." last="Maki">Robert G. Maki</name><affiliation><nlm:aff id="A8">Department of Medicine/Pediatrics, Mount Sinai School of Medicine, New York, NY, USA</nlm:aff></affiliation></author><author><name sortKey="Coindre, Jean Michel" sort="Coindre, Jean Michel" uniqKey="Coindre J" first="Jean-Michel" last="Coindre">Jean-Michel Coindre</name><affiliation><nlm:aff id="A9">Department of Pathology, Institut Bergonié, Bordeaux, France</nlm:aff></affiliation></author><author><name sortKey="Antonescu, Cristina R" sort="Antonescu, Cristina R" uniqKey="Antonescu C" first="Cristina R." last="Antonescu">Cristina R. Antonescu</name><affiliation><nlm:aff id="A1">Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY</nlm:aff></affiliation></author></analytic><series><title level="j">Cancer</title><idno type="ISSN">0008-543X</idno><idno type="eISSN">1097-0142</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S1"><title>Background</title><p id="P3">The p53 and the PIK3CA/AKT/mTOR pathways are frequently altered in sarcoma with complex genomics such as leiomyosarcoma (LMS) or undifferentiated pleomorphic sarcoma (UPS). The scale of genetic abnormalities in these pathways remains unknown in angiosarcoma.</p></sec><sec id="S2"><title>Methods</title><p id="P4">We investigated the status of critical genes involved in the p53 and the PIK3CA/AKT/mTOR pathways in a series of 62 AS.</p></sec><sec id="S3"><title>Results</title><p id="P5">The mutation and deletion rates of <italic>TP53</italic> were 4% and 0, respectively. p53 overexpression was detected by immunohistochemistry in 49% of cases and was associated with inferior disease-free survival. Although p14 inactivation or HDM2 overexpression are frequent in LMS and UPS and could substitute for <italic>TP53</italic> mutation or deletion, such alterations were rare in angiosarcomas. pS6K and/or p-4eBP1 overexpression was observed in 42% of cases suggesting frequent activation of the PIK3CA/AKT/mTOR pathway in angiosarcomas. Activation was not related to intragenic deletion of <italic>PTEN</italic>, an aberration that is frequent in LMS and UPS, but absent in angiosarcomas.</p></sec><sec id="S4"><title>Conclusion</title><p id="P6">Angiosarcomas constitute a distinct subgroup among sarcomas with complex genomics. Although <italic>TP53</italic> mutation and <italic>PTEN</italic> deletion are frequent in LMS and UPS, these aberrations are rarely involved in the pathogenesis of AS.</p></sec></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">0374236</journal-id><journal-id journal-id-type="pubmed-jr-id">2771</journal-id><journal-id journal-id-type="nlm-ta">Cancer</journal-id><journal-id journal-id-type="iso-abbrev">Cancer</journal-id><journal-title-group><journal-title>Cancer</journal-title></journal-title-group><issn pub-type="ppub">0008-543X</issn><issn pub-type="epub">1097-0142</issn></journal-meta><article-meta><article-id pub-id-type="pmid">22648906</article-id><article-id pub-id-type="pmc">3434269</article-id><article-id pub-id-type="doi">10.1002/cncr.27614</article-id><article-id pub-id-type="manuscript">NIHMS369434</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Alterations of p53 and PIK3CA/AKT/mTOR Pathways in Angiosarcomas: A Pattern Distinct from Other Sarcomas with Complex Genomics</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Italiano</surname><given-names>Antoine</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="author-notes" rid="FN1">∞</xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Chun-Liang</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Thomas</surname><given-names>Rachael</given-names></name><xref ref-type="aff" rid="A3">3</xref><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Breen</surname><given-names>Matthew</given-names></name><xref ref-type="aff" rid="A3">3</xref><xref ref-type="aff" rid="A4">4</xref><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Bonnet</surname><given-names>Françoise</given-names></name><xref ref-type="aff" rid="A6">6</xref><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Sevenet</surname><given-names>Nicolas</given-names></name><xref ref-type="aff" rid="A6">6</xref><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Longy</surname><given-names>Michel</given-names></name><xref ref-type="aff" rid="A6">6</xref><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Maki</surname><given-names>Robert G.</given-names></name><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Coindre</surname><given-names>Jean-Michel</given-names></name><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author"><name><surname>Antonescu</surname><given-names>Cristina R.</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="corresp" rid="CR1">*</xref></contrib></contrib-group><aff id="A1"><label>1</label>Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY</aff><aff id="A2"><label>2</label>Department of Medical Oncology, Institute Bergonié, Bordeaux, France</aff><aff id="A3"><label>3</label>Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC</aff><aff id="A4"><label>4</label>Center for Comparative Medicine and Translational Research, North Carolina State University, Raleigh, NC</aff><aff id="A5"><label>5</label>Cancer Genetics Program, UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC</aff><aff id="A6"><label>6</label>INSERM U916, University of Bordeaux, France</aff><aff id="A7"><label>7</label>Cancer Genetics Unit, Institut Bergonié, Bordeaux, France</aff><aff id="A8"><label>8</label>Department of Medicine/Pediatrics, Mount Sinai School of Medicine, New York, NY, USA</aff><aff id="A9"><label>9</label>Department of Pathology, Institut Bergonié, Bordeaux, France</aff><author-notes><fn id="FN1"><label>∞</label><p id="P1">Visiting Research Fellow from the Bergonie Institute, Bordeaux, France</p></fn><fn id="FN2"><p id="P2">Antoine Italiano, MD, PhD, Department of Medical Oncology, Institut Bergonié, 229 Cours de l’Argonne, 33000 Bordeaux, France. <email>italiano@bergonie.org</email></p></fn><corresp id="CR1"><label>*</label><bold>Correspondence</bold>: Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. <email>antonesc@mskcc.org</email>;
</corresp></author-notes><pub-date pub-type="nihms-submitted"><day>17</day><month>5</month><year>2012</year></pub-date><pub-date pub-type="epub"><day>30</day><month>5</month><year>2012</year></pub-date><pub-date pub-type="ppub"><day>1</day><month>12</month><year>2012</year></pub-date><pub-date pub-type="pmc-release"><day>01</day><month>12</month><year>2013</year></pub-date><volume>118</volume><issue>23</issue><fpage>5878</fpage><lpage>5887</lpage><abstract><sec id="S1"><title>Background</title><p id="P3">The p53 and the PIK3CA/AKT/mTOR pathways are frequently altered in sarcoma with complex genomics such as leiomyosarcoma (LMS) or undifferentiated pleomorphic sarcoma (UPS). The scale of genetic abnormalities in these pathways remains unknown in angiosarcoma.</p></sec><sec id="S2"><title>Methods</title><p id="P4">We investigated the status of critical genes involved in the p53 and the PIK3CA/AKT/mTOR pathways in a series of 62 AS.</p></sec><sec id="S3"><title>Results</title><p id="P5">The mutation and deletion rates of <italic>TP53</italic> were 4% and 0, respectively. p53 overexpression was detected by immunohistochemistry in 49% of cases and was associated with inferior disease-free survival. Although p14 inactivation or HDM2 overexpression are frequent in LMS and UPS and could substitute for <italic>TP53</italic> mutation or deletion, such alterations were rare in angiosarcomas. pS6K and/or p-4eBP1 overexpression was observed in 42% of cases suggesting frequent activation of the PIK3CA/AKT/mTOR pathway in angiosarcomas. Activation was not related to intragenic deletion of <italic>PTEN</italic>, an aberration that is frequent in LMS and UPS, but absent in angiosarcomas.</p></sec><sec id="S4"><title>Conclusion</title><p id="P6">Angiosarcomas constitute a distinct subgroup among sarcomas with complex genomics. Although <italic>TP53</italic> mutation and <italic>PTEN</italic> deletion are frequent in LMS and UPS, these aberrations are rarely involved in the pathogenesis of AS.</p></sec></abstract><kwd-group><kwd>angiosarcoma</kwd><kwd><italic>TP53</italic></kwd><kwd><italic>PIK3CA</italic></kwd><kwd>PTEN</kwd><kwd><italic>MDM2</italic></kwd><kwd><italic>P14</italic></kwd><kwd><italic>BRAF</italic></kwd><kwd><italic>NRAS</italic></kwd></kwd-group><funding-group><award-group><funding-source country="United States">National Cancer Institute : NCI</funding-source><award-id>P01 CA047179 || CA</award-id></award-group><award-group><funding-source country="United States">National Cancer Institute : NCI</funding-source><award-id>P01 CA047179 || CA</award-id></award-group><award-group><funding-source country="United States">National Cancer Institute : NCI</funding-source><award-id>P01 CA047179 || CA</award-id></award-group><award-group><funding-source country="United States">National Cancer Institute : NCI</funding-source><award-id>P01 CA047179 || CA</award-id></award-group><award-group><funding-source country="United States">National Cancer Institute : NCI</funding-source><award-id>P01 CA047179 || CA</award-id></award-group><award-group><funding-source country="United States">National Cancer Institute : NCI</funding-source><award-id>P01 CA047179 || CA</award-id></award-group><award-group><funding-source country="United States">National Cancer Institute : NCI</funding-source><award-id>P01 CA047179 || CA</award-id></award-group><award-group><funding-source country="United States">National Cancer Institute : NCI</funding-source><award-id>P01 CA047179 || CA</award-id></award-group><award-group><funding-source country="United States">National Cancer Institute : NCI</funding-source><award-id>P01 CA047179 || CA</award-id></award-group><award-group><funding-source country="United States">National Cancer Institute : NCI</funding-source><award-id>P01 CA047179 || CA</award-id></award-group><award-group><funding-source country="United States">National Cancer Institute : NCI</funding-source><award-id>P01 CA047179 || CA</award-id></award-group><award-group><funding-source country="United States">National Cancer Institute : NCI</funding-source><award-id>P01 CA047179 || CA</award-id></award-group></funding-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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