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Germline Mutations of Inhibins in Early-Onset Ovarian Epithelial Tumors

Isabelle Tournier 1 Régine Marlin 1 Kelly Walton 2 Francoise Charbonnier 1 Sophie Coutant 1 Jean-Christophe Thery 1 Camille Charbonnier 1 Cailyn Spurrell 3 Myriam Vezain 1 Lorena Ippolito 1 Gaëlle Bougeard 1 Horace Roman 4 Julie Tinat 1, 5 Jean-Christophe Sabourin 6 Dominique Stoppa-Lyonnet 7 Olivier Caron 8 Brigitte Bressac-de Paillerets 8 Dominique Vaur 9 Mary-Claire King 3 Craig Harrison 2 Thierry Frebourg 1, 5
1 GMFC - Génétique du cancer et des maladies neuropsychiatriques
2 Prince Henry's Institute of Medical Research [Clayton, Australia]
3 Departments of Medicine (Medical Genetics) and Genome Sciences
4 Service de gynécologie et obstétrique [CHU Rouen]
5 Centre Normandie de Génomique et de Médecine Personnalisée - Département de génétique [CHU Rouen]
6 Département de Pathologie [CHU Rouen]
7 U830 - Unité de génétique et biologie des cancers
8 IGR - Institut Gustave Roussy
9 UNICANCER/CRLC - Centre Régional de Lutte contre le Cancer François Baclesse [Caen]
Abstract : To identify novel genetic bases of early-onsetepithelial ovarian tumors, we used the trio exome sequencing strategy in a patient without familial history of cancerwho presented metastatic serous ovarian adenocarcinomasat 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 akey role in ovarian development. In vitro, this mutation alters the ratio of secreted activins and inhibins. In a secondpatient with early-onset serous borderline papillary cystadenoma, we identified an unreported germline mutation(c.179G>T/p.Arg60Leu) of the INHA gene encoding theα-subunit, the partner of the βA-subunit. This mutationalso alters the secreted activin/inhibin ratio, by disruptingboth inhibin A and inhibin B biosynthesis. In a cohort of62 cases, we detected an additional unreported germlinemutation of the INHBA gene (c.839G>A/p.Gly280Glu).Our results strongly suggest that inhibin mutations contribute to the genetic determinism of epithelial ovariantumors.
Keywords : INHA Activin Exome Inhibin Ovary Cancer INHBA
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Submitted on : Thursday, May 27, 2021 - 2:31:13 PM
Last modification on : Wednesday, October 27, 2021 - 4:13:12 PM
Long-term archiving on: : Saturday, August 28, 2021 - 7:24:47 PM

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FNCLCC | UNIV-PARIS5 | IGR | GPMCND | UNIROUEN | COMUE-NORMANDIE | CURIE | BACLESSE | PSL | INSERM | UNIV-PARIS

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Isabelle Tournier, Régine Marlin, Kelly Walton, Francoise Charbonnier, Sophie Coutant, et al.. Germline Mutations of Inhibins in Early-Onset Ovarian Epithelial Tumors. Human Mutation, Wiley, 2014, 35 (3), pp.294-297. ⟨10.1002/humu.22489⟩. ⟨hal-02375836⟩

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