Germline Mutations of Inhibins in Early‐Onset Ovarian Epithelial Tumors
Identifieur interne : 003D97 ( Main/Exploration ); précédent : 003D96; suivant : 003D98Germline Mutations of Inhibins in Early‐Onset Ovarian Epithelial Tumors
Auteurs : Isabelle Tournier [France] ; Régine Marlin [France] ; Kelly Walton [Australie] ; Françoise Charbonnier [France] ; Sophie Coutant [France] ; Jean-Christophe Théry [France] ; Camille Charbonnier [France] ; Cailyn Spurrell ; Myriam Vezain [France] ; Lorena Ippolito [France] ; Gaëlle Bougeard [France] ; Horace Roman [France] ; Julie Tinat [France] ; Jean-Christophe Sabourin [France] ; Dominique Stoppa-Lyonnet [France] ; Olivier Caron [France] ; Brigitte Bressac-De Paillerets [France] ; Dominique Vaur [France] ; Mary-Claire King ; Craig Harrison [Australie] ; Thierry Frebourg [France]Source :
- Human Mutation [ 1059-7794 ] ; 2014-03.
Abstract
To identify novel genetic bases of early‐onset epithelial ovarian tumors, we used the trio exome sequencing strategy in a patient without familial history of cancer who presented metastatic serous ovarian adenocarcinomas at 21 years of age. We identified a single de novo mutation (c.1157A>G/p.Asn386Ser) within the INHBA gene encoding the βA‐subunit of inhibins/activins, which play a key role in ovarian development. In vitro, this mutation alters the ratio of secreted activins and inhibins. In a second patient with early‐onset serous borderline papillary cystadenoma, we identified an unreported germline mutation (c.179G>T/p.Arg60Leu) of the INHA gene encoding the α‐subunit, the partner of the βA‐subunit. This mutation also alters the secreted activin/inhibin ratio, by disrupting both inhibin A and inhibin B biosynthesis. In a cohort of 62 cases, we detected an additional unreported germline mutation of the INHBA gene (c.839G>A/p.Gly280Glu). Our results strongly suggest that inhibin mutations contribute to the genetic determinism of epithelial ovarian tumors.
Url:
- https://api.istex.fr/document/136B0BC49B1DB2C491E7936F018CE476D5FE2971/fulltext/pdf
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4284000
DOI: 10.1002/humu.22489
Affiliations:
- Australie, France
- Basse-Normandie, Haute-Normandie, Région Normandie, Île-de-France
- Caen, Paris, Rouen
Links toward previous steps (curation, corpus...)
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- to stream Main, to step Curation: 003D97
Le document en format XML
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King</name><affiliation><wicri:noCountry code="subField">Seattle</wicri:noCountry></affiliation></author><author><name sortKey="Harrison, Craig" sort="Harrison, Craig" uniqKey="Harrison C" first="Craig" last="Harrison">Craig Harrison</name><affiliation wicri:level="1"><country xml:lang="fr">Australie</country><wicri:regionArea>Growth Factor Signalling Laboratory, Prince Henry's Institute of Medical Research, Clayton</wicri:regionArea><wicri:noRegion>Clayton</wicri:noRegion></affiliation></author><author><name sortKey="Frebourg, Thierry" sort="Frebourg, Thierry" uniqKey="Frebourg T" first="Thierry" last="Frebourg">Thierry Frebourg</name><affiliation wicri:level="1"><country xml:lang="fr">France</country><wicri:regionArea>Inserm U1079, Institute for Research and Innovation in Biomedicine, University of Rouen, Rouen, Cancéropôle Nord‐Ouest</wicri:regionArea><wicri:noRegion>Cancéropôle Nord‐Ouest</wicri:noRegion><wicri:noRegion>Cancéropôle Nord‐Ouest</wicri:noRegion></affiliation><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Department of Genetics, University Hospital of Rouen, Rouen</wicri:regionArea><placeName><region type="region">Région Normandie</region><region type="old region">Haute-Normandie</region><settlement type="city">Rouen</settlement></placeName></affiliation><affiliation wicri:level="1"><country wicri:rule="url">France</country></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Human Mutation</title><title level="j" type="alt">HUMAN MUTATION</title><idno type="ISSN">1059-7794</idno><idno type="eISSN">1098-1004</idno><imprint><biblScope unit="vol">35</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="294">294</biblScope><biblScope unit="page" to="297">297</biblScope><biblScope unit="page-count">4</biblScope><date type="published" when="2014-03">2014-03</date></imprint><idno type="ISSN">1059-7794</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1059-7794</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">To identify novel genetic bases of early‐onset epithelial ovarian tumors, we used the trio exome sequencing strategy in a patient without familial history of cancer who presented metastatic serous ovarian adenocarcinomas at 21 years of age. We identified a single de novo mutation (c.1157A>G/p.Asn386Ser) within the INHBA gene encoding the βA‐subunit of inhibins/activins, which play a key role in ovarian development. In vitro, this mutation alters the ratio of secreted activins and inhibins. In a second patient with early‐onset serous borderline papillary cystadenoma, we identified an unreported germline mutation (c.179G>T/p.Arg60Leu) of the INHA gene encoding the α‐subunit, the partner of the βA‐subunit. This mutation also alters the secreted activin/inhibin ratio, by disrupting both inhibin A and inhibin B biosynthesis. In a cohort of 62 cases, we detected an additional unreported germline mutation of the INHBA gene (c.839G>A/p.Gly280Glu). Our results strongly suggest that inhibin mutations contribute to the genetic determinism of epithelial ovarian tumors.</div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li></country><region><li>Basse-Normandie</li><li>Haute-Normandie</li><li>Région Normandie</li><li>Île-de-France</li></region><settlement><li>Caen</li><li>Paris</li><li>Rouen</li></settlement></list><tree><noCountry><name sortKey="King, Mary Laire" sort="King, Mary Laire" uniqKey="King M" first="Mary-Claire" last="King">Mary-Claire King</name><name sortKey="Spurrell, Cailyn" sort="Spurrell, Cailyn" uniqKey="Spurrell C" first="Cailyn" last="Spurrell">Cailyn Spurrell</name></noCountry><country name="France"><region name="Région Normandie"><name sortKey="Tournier, Isabelle" sort="Tournier, Isabelle" uniqKey="Tournier I" first="Isabelle" last="Tournier">Isabelle Tournier</name></region><name sortKey="Bougeard, Gaelle" sort="Bougeard, Gaelle" uniqKey="Bougeard G" first="Gaëlle" last="Bougeard">Gaëlle Bougeard</name><name sortKey="Bressac E Paillerets, Brigitte" sort="Bressac E Paillerets, Brigitte" uniqKey="Bressac E Paillerets B" first="Brigitte" last="Bressac-De Paillerets">Brigitte Bressac-De Paillerets</name><name sortKey="Caron, Olivier" sort="Caron, Olivier" uniqKey="Caron O" first="Olivier" last="Caron">Olivier Caron</name><name sortKey="Charbonnier, Camille" sort="Charbonnier, Camille" uniqKey="Charbonnier C" first="Camille" last="Charbonnier">Camille Charbonnier</name><name sortKey="Charbonnier, Francoise" sort="Charbonnier, Francoise" uniqKey="Charbonnier F" first="Françoise" last="Charbonnier">Françoise Charbonnier</name><name sortKey="Coutant, Sophie" sort="Coutant, Sophie" uniqKey="Coutant S" first="Sophie" last="Coutant">Sophie Coutant</name><name sortKey="Frebourg, Thierry" sort="Frebourg, Thierry" uniqKey="Frebourg T" first="Thierry" last="Frebourg">Thierry Frebourg</name><name sortKey="Frebourg, Thierry" sort="Frebourg, Thierry" uniqKey="Frebourg T" first="Thierry" last="Frebourg">Thierry Frebourg</name><name sortKey="Frebourg, Thierry" sort="Frebourg, Thierry" uniqKey="Frebourg T" first="Thierry" last="Frebourg">Thierry Frebourg</name><name sortKey="Ippolito, Lorena" sort="Ippolito, Lorena" uniqKey="Ippolito L" first="Lorena" last="Ippolito">Lorena Ippolito</name><name sortKey="Marlin, Regine" sort="Marlin, Regine" uniqKey="Marlin R" first="Régine" last="Marlin">Régine Marlin</name><name sortKey="Roman, Horace" sort="Roman, Horace" uniqKey="Roman H" first="Horace" last="Roman">Horace Roman</name><name sortKey="Sabourin, Jean Hristophe" sort="Sabourin, Jean Hristophe" uniqKey="Sabourin J" first="Jean-Christophe" last="Sabourin">Jean-Christophe Sabourin</name><name sortKey="Stoppa Yonnet, Dominique" sort="Stoppa Yonnet, Dominique" uniqKey="Stoppa Yonnet D" first="Dominique" last="Stoppa-Lyonnet">Dominique Stoppa-Lyonnet</name><name sortKey="Thery, Jean Hristophe" sort="Thery, Jean Hristophe" uniqKey="Thery J" first="Jean-Christophe" last="Théry">Jean-Christophe Théry</name><name sortKey="Tinat, Julie" sort="Tinat, Julie" uniqKey="Tinat J" first="Julie" last="Tinat">Julie Tinat</name><name sortKey="Tinat, Julie" sort="Tinat, Julie" uniqKey="Tinat J" first="Julie" last="Tinat">Julie Tinat</name><name sortKey="Vaur, Dominique" sort="Vaur, Dominique" uniqKey="Vaur D" first="Dominique" last="Vaur">Dominique Vaur</name><name sortKey="Vezain, Myriam" sort="Vezain, Myriam" uniqKey="Vezain M" first="Myriam" last="Vezain">Myriam Vezain</name></country><country name="Australie"><noRegion><name sortKey="Walton, Kelly" sort="Walton, Kelly" uniqKey="Walton K" first="Kelly" last="Walton">Kelly Walton</name></noRegion><name sortKey="Harrison, Craig" sort="Harrison, Craig" uniqKey="Harrison C" first="Craig" last="Harrison">Craig Harrison</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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