Germline mutations of inhibins in early-onset ovarian epithelial tumors

Isabelle Tournier, Régine Marlin, Kelly Walton, Françoise Charbonnier, Sophie Coutant, Jean-Christophe Théry, Camille Charbonnier, Cailyn Spurrell, Myriam Vezain, Lorena Ippolito, Gaëlle Bougeard, Horace Roman, Julie Tinat, Jean-Christophe Sabourin, Dominique Stoppa-Lyonnet, Olivier Caron, Brigitte Bressac-de Paillerets, Dominique Vaur, Mary-Claire King, Craig HarrisonThierry Frebourg

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10 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)294-297
Number of pages4
JournalHuman Mutation
Issue number3
Publication statusPublished - Mar 2014
Externally publishedYes


  • Activin
  • Cancer
  • Exome
  • INHA
  • Inhibin
  • Ovary

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