Cripto: Expression, epigenetic regulation and potential diagnostic use in testicular germ cell tumors
Identifieur interne : 001A32 ( Pmc/Corpus ); précédent : 001A31; suivant : 001A33Cripto: Expression, epigenetic regulation and potential diagnostic use in testicular germ cell tumors
Auteurs : Cassy M. Spiller ; Ad J. M. Gillis ; Guillaume Burnet ; Hans Stoop ; Peter Koopman ; Josephine Bowles ; Leendert H. J. LooijengaSource :
- Molecular Oncology [ 1574-7891 ] ; 2015.
Abstract
Type II germ cell tumors arise after puberty from a germ cell that was incorrectly programmed during fetal life. Failure of testicular germ cells to properly differentiate can lead to the formation of germ cell neoplasia in situ of the testis; this precursor cell invariably gives rise to germ cell cancer after puberty. The Nodal co‐receptor Cripto is expressed transiently during normal germ cell development and is ectopically expressed in non‐seminomas that arise from germ cell neoplasia in situ, suggesting that its aberrant expression may underlie germ cell dysregulation and hence germ cell cancer. Here we investigated methylation of the Cripto promoter in mouse germ cells and human germ cell cancer and correlated this with the level of CRIPTO protein expression. We found hypomethylation of the CRIPTO promoter in undifferentiated fetal germ cells, embryonal carcinoma and seminomas, but hypermethylation in differentiated fetal germ cells and the differentiated types of non‐seminomas. CRIPTO protein was strongly expressed in germ cell neoplasia in situ along with embryonal carcinoma, yolk sac tumor and seminomas. Further, cleaved CRIPTO was detected in media from seminoma and embryonal carcinoma cell lines, suggesting that cleaved CRIPTO may provide diagnostic indication of germ cell cancer. Accordingly, CRIPTO was detectable in serum from 6/15 patients with embryonal carcinoma, 5/15 patients with seminoma, 4/5 patients with germ cell neoplasia in situ cells only and in 1/15 control patients. These findings suggest that CRIPTO expression may be a useful serological marker for diagnostic and/or prognostic purposes during germ cell cancer management.
Url:
DOI: 10.1016/j.molonc.2015.11.003
PubMed: 26654129
PubMed Central: 5423140
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Gillis</name><affiliation><nlm:aff id="mol22016104526-aff-0002"></nlm:aff></affiliation></author><author><name sortKey="Burnet, Guillaume" sort="Burnet, Guillaume" uniqKey="Burnet G" first="Guillaume" last="Burnet">Guillaume Burnet</name><affiliation><nlm:aff id="mol22016104526-aff-0001"></nlm:aff></affiliation><affiliation><nlm:aff id="mol22016104526-aff-0003"></nlm:aff></affiliation></author><author><name sortKey="Stoop, Hans" sort="Stoop, Hans" uniqKey="Stoop H" first="Hans" last="Stoop">Hans Stoop</name><affiliation><nlm:aff id="mol22016104526-aff-0002"></nlm:aff></affiliation></author><author><name sortKey="Koopman, Peter" sort="Koopman, Peter" uniqKey="Koopman P" first="Peter" last="Koopman">Peter Koopman</name><affiliation><nlm:aff id="mol22016104526-aff-0001"></nlm:aff></affiliation></author><author><name sortKey="Bowles, Josephine" sort="Bowles, Josephine" uniqKey="Bowles J" first="Josephine" last="Bowles">Josephine Bowles</name><affiliation><nlm:aff id="mol22016104526-aff-0001"></nlm:aff></affiliation></author><author><name sortKey="Looijenga, Leendert H J" sort="Looijenga, Leendert H J" uniqKey="Looijenga L" first="Leendert H. 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Spiller</name><affiliation><nlm:aff id="mol22016104526-aff-0001"></nlm:aff></affiliation></author><author><name sortKey="Gillis, Ad J M" sort="Gillis, Ad J M" uniqKey="Gillis A" first="Ad J. M." last="Gillis">Ad J. M. Gillis</name><affiliation><nlm:aff id="mol22016104526-aff-0002"></nlm:aff></affiliation></author><author><name sortKey="Burnet, Guillaume" sort="Burnet, Guillaume" uniqKey="Burnet G" first="Guillaume" last="Burnet">Guillaume Burnet</name><affiliation><nlm:aff id="mol22016104526-aff-0001"></nlm:aff></affiliation><affiliation><nlm:aff id="mol22016104526-aff-0003"></nlm:aff></affiliation></author><author><name sortKey="Stoop, Hans" sort="Stoop, Hans" uniqKey="Stoop H" first="Hans" last="Stoop">Hans Stoop</name><affiliation><nlm:aff id="mol22016104526-aff-0002"></nlm:aff></affiliation></author><author><name sortKey="Koopman, Peter" sort="Koopman, Peter" uniqKey="Koopman P" first="Peter" last="Koopman">Peter Koopman</name><affiliation><nlm:aff id="mol22016104526-aff-0001"></nlm:aff></affiliation></author><author><name sortKey="Bowles, Josephine" sort="Bowles, Josephine" uniqKey="Bowles J" first="Josephine" last="Bowles">Josephine Bowles</name><affiliation><nlm:aff id="mol22016104526-aff-0001"></nlm:aff></affiliation></author><author><name sortKey="Looijenga, Leendert H J" sort="Looijenga, Leendert H J" uniqKey="Looijenga L" first="Leendert H. J." last="Looijenga">Leendert H. J. Looijenga</name><affiliation><nlm:aff id="mol22016104526-aff-0002"></nlm:aff></affiliation></author></analytic><series><title level="j">Molecular Oncology</title><idno type="ISSN">1574-7891</idno><idno type="eISSN">1878-0261</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Type II germ cell tumors arise after puberty from a germ cell that was incorrectly programmed during fetal life. Failure of testicular germ cells to properly differentiate can lead to the formation of germ cell neoplasia in situ of the testis; this precursor cell invariably gives rise to germ cell cancer after puberty. The Nodal co‐receptor Cripto is expressed transiently during normal germ cell development and is ectopically expressed in non‐seminomas that arise from germ cell neoplasia in situ, suggesting that its aberrant expression may underlie germ cell dysregulation and hence germ cell cancer. Here we investigated methylation of the Cripto promoter in mouse germ cells and human germ cell cancer and correlated this with the level of CRIPTO protein expression. We found hypomethylation of the CRIPTO promoter in undifferentiated fetal germ cells, embryonal carcinoma and seminomas, but hypermethylation in differentiated fetal germ cells and the differentiated types of non‐seminomas. CRIPTO protein was strongly expressed in germ cell neoplasia in situ along with embryonal carcinoma, yolk sac tumor and seminomas. Further, cleaved CRIPTO was detected in media from seminoma and embryonal carcinoma cell lines, suggesting that cleaved CRIPTO may provide diagnostic indication of germ cell cancer. Accordingly, CRIPTO was detectable in serum from 6/15 patients with embryonal carcinoma, 5/15 patients with seminoma, 4/5 patients with germ cell neoplasia in situ cells only and in 1/15 control patients. These findings suggest that CRIPTO expression may be a useful serological marker for diagnostic and/or prognostic purposes during germ cell cancer management.</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>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Mol Oncol</journal-id><journal-id journal-id-type="iso-abbrev">Mol Oncol</journal-id><journal-id journal-id-type="doi">10.1002/(ISSN)1878-0261</journal-id><journal-id journal-id-type="publisher-id">MOL2</journal-id><journal-title-group><journal-title>Molecular Oncology</journal-title></journal-title-group><issn pub-type="ppub">1574-7891</issn><issn pub-type="epub">1878-0261</issn><publisher><publisher-name>John Wiley and Sons Inc.</publisher-name><publisher-loc>Hoboken</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26654129</article-id><article-id pub-id-type="pmc">5423140</article-id><article-id pub-id-type="doi">10.1016/j.molonc.2015.11.003</article-id><article-id pub-id-type="publisher-id">MOL22016104526</article-id><article-categories><subj-group subj-group-type="overline"><subject>Article</subject></subj-group><subj-group subj-group-type="heading"><subject>Articles</subject></subj-group></article-categories><title-group><article-title>Cripto: Expression, epigenetic regulation and potential diagnostic use in testicular germ cell tumors</article-title></title-group><contrib-group><contrib id="mol22016104526-cr-0001" contrib-type="author"><name><surname>Spiller</surname><given-names>Cassy M.</given-names></name><xref ref-type="aff" rid="mol22016104526-aff-0001"><sup>1</sup></xref></contrib><contrib id="mol22016104526-cr-0002" contrib-type="author"><name><surname>Gillis</surname><given-names>Ad J.M.</given-names></name><xref ref-type="aff" rid="mol22016104526-aff-0002"><sup>2</sup></xref></contrib><contrib id="mol22016104526-cr-0003" contrib-type="author"><name><surname>Burnet</surname><given-names>Guillaume</given-names></name><xref ref-type="aff" rid="mol22016104526-aff-0001"><sup>1</sup></xref><xref ref-type="aff" rid="mol22016104526-aff-0003"><sup>3</sup></xref></contrib><contrib id="mol22016104526-cr-0004" contrib-type="author"><name><surname>Stoop</surname><given-names>Hans</given-names></name><xref ref-type="aff" rid="mol22016104526-aff-0002"><sup>2</sup></xref></contrib><contrib id="mol22016104526-cr-0005" contrib-type="author"><name><surname>Koopman</surname><given-names>Peter</given-names></name><xref ref-type="aff" rid="mol22016104526-aff-0001"><sup>1</sup></xref></contrib><contrib id="mol22016104526-cr-0006" contrib-type="author"><name><surname>Bowles</surname><given-names>Josephine</given-names></name><xref ref-type="aff" rid="mol22016104526-aff-0001"><sup>1</sup></xref><xref ref-type="author-notes" rid="mol22016104526-note-fn1"><sup>†</sup></xref></contrib><contrib id="mol22016104526-cr-0007" contrib-type="author" corresp="yes"><name><surname>Looijenga</surname><given-names>Leendert H.J.</given-names></name><address><email>l.looijenga@erasmusmc.nl</email></address><xref ref-type="aff" rid="mol22016104526-aff-0002"><sup>2</sup></xref><xref ref-type="author-notes" rid="mol22016104526-note-fn1"><sup>†</sup></xref></contrib></contrib-group><aff id="mol22016104526-aff-0001"><label><sup>1</sup></label>Division of Genomics of Development and Disease, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia</aff><aff id="mol22016104526-aff-0002"><label><sup>2</sup></label>Department of Pathology, Erasmus MC – University Medical Center, Rotterdam, 3015, The Netherlands</aff><aff id="mol22016104526-aff-0003"><label><sup>3</sup></label>Departement de Biologie, Ecole Normale Superieure de Cachan, Cachan, France</aff><author-notes><corresp id="correspondenceTo"><label>*</label>Corresponding author.</corresp><fn id="mol22016104526-note-fn1"><label>†</label><p>Joint senior authors.</p></fn></author-notes><pub-date pub-type="epub"><day>18</day><month>11</month><year>2015</year></pub-date><pub-date pub-type="ppub"><month>4</month><year>2016</year></pub-date><volume>10</volume><issue>4</issue><issue-id pub-id-type="doi">10.1002/mol2.2016.10.issue-4</issue-id><fpage>526</fpage><lpage>537</lpage><history><date date-type="received"><day>18</day><month>6</month><year>2015</year></date><date date-type="rev-recd"><day>03</day><month>11</month><year>2015</year></date><date date-type="accepted"><day>03</day><month>11</month><year>2015</year></date></history><permissions><pmc-comment> © Federation of European Biochemical Societies </pmc-comment>
<copyright-statement content-type="article-copyright">© 2016 Federation of European Biochemical Societies</copyright-statement></permissions><self-uri content-type="pdf" xlink:type="simple" xlink:href="file:MOL2-10-526.pdf"></self-uri><abstract id="mol22016104526-abs-0001"><p>Type II germ cell tumors arise after puberty from a germ cell that was incorrectly programmed during fetal life. Failure of testicular germ cells to properly differentiate can lead to the formation of germ cell neoplasia in situ of the testis; this precursor cell invariably gives rise to germ cell cancer after puberty. The Nodal co‐receptor Cripto is expressed transiently during normal germ cell development and is ectopically expressed in non‐seminomas that arise from germ cell neoplasia in situ, suggesting that its aberrant expression may underlie germ cell dysregulation and hence germ cell cancer. Here we investigated methylation of the Cripto promoter in mouse germ cells and human germ cell cancer and correlated this with the level of CRIPTO protein expression. We found hypomethylation of the CRIPTO promoter in undifferentiated fetal germ cells, embryonal carcinoma and seminomas, but hypermethylation in differentiated fetal germ cells and the differentiated types of non‐seminomas. CRIPTO protein was strongly expressed in germ cell neoplasia in situ along with embryonal carcinoma, yolk sac tumor and seminomas. Further, cleaved CRIPTO was detected in media from seminoma and embryonal carcinoma cell lines, suggesting that cleaved CRIPTO may provide diagnostic indication of germ cell cancer. Accordingly, CRIPTO was detectable in serum from 6/15 patients with embryonal carcinoma, 5/15 patients with seminoma, 4/5 patients with germ cell neoplasia in situ cells only and in 1/15 control patients. These findings suggest that CRIPTO expression may be a useful serological marker for diagnostic and/or prognostic purposes during germ cell cancer management.</p></abstract><abstract abstract-type="short" id="mol22016104526-abs-0002"><title>Highlights</title><p><list list-type="bullet"><list-item><p>Promoter methylation of CRIPTO is differentially regulated between normal germ cell development and in germ cell tumors.</p></list-item><list-item><p>CRIPTO is strongly expressed in the germ cell precursor cell GCNIS, EC, YST and SE.</p></list-item><list-item><p>CRIPTO protein is cleaved from the cell surface and detectable in serum of patients with GCNIS‐only, EC, YST and SE.</p></list-item></list></p></abstract><kwd-group><kwd id="mol22016104526-kwd-0001">Cripto</kwd><kwd id="mol22016104526-kwd-0002">Testicular germ cell cancer</kwd><kwd id="mol22016104526-kwd-0003">Methylation</kwd><kwd id="mol22016104526-kwd-0004">Diagnostic</kwd></kwd-group><counts><fig-count count="6"></fig-count><table-count count="1"></table-count><equation-count count="0"></equation-count><ref-count count="40"></ref-count><page-count count="12"></page-count><word-count count="8961"></word-count></counts><custom-meta-group><custom-meta><meta-name>source-schema-version-number</meta-name><meta-value>2.0</meta-value></custom-meta><custom-meta><meta-name>component-id</meta-name><meta-value>mol22016104526</meta-value></custom-meta><custom-meta><meta-name>cover-date</meta-name><meta-value>April 2016</meta-value></custom-meta><custom-meta><meta-name>details-of-publishers-convertor</meta-name><meta-value>Converter:WILEY_ML3GV2_TO_NLMPMC version:5.0.9 mode:remove_FC converted:26.04.2017</meta-value></custom-meta></custom-meta-group></article-meta><notes><p content-type="self-citation"><mixed-citation publication-type="journal" id="mol22016104526-cit-0000"><string-name><surname>Spiller</surname><given-names>Cassy M.</given-names></string-name>,
<string-name><surname>Gillis</surname><given-names>Ad J.M.</given-names></string-name>,
<string-name><surname>Burnet</surname><given-names>Guillaume</given-names></string-name>,
<string-name><surname>Stoop</surname><given-names>Hans</given-names></string-name>,
<string-name><surname>Koopman</surname><given-names>Peter</given-names></string-name>,
<string-name><surname>Bowles</surname><given-names>Josephine</given-names></string-name>,
<string-name><surname>Looijenga</surname><given-names>Leendert H.J.</given-names></string-name>,
(<year>2016</year>),
<article-title>Cripto: Expression, epigenetic regulation and potential diagnostic use in testicular germ cell tumors</article-title>,
<source>Molecular Oncology</source>,
<volume>10</volume>, doi: 10.1016/j.molonc.2015.11.003.</mixed-citation></p></notes></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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